Products
Bendamustine is commercially available as a lyophilizate for the preparation of an infusion solution (ribomustine). It actually has good oral bioavailability when taken fasting, but is only administered parenterally. Generic drugs are registered. Bendamustine was developed in 1963 by Ozegowski et al. in Jena in what was then East Germany and was marketed only in Germany until the 1990s. In the 1990s, it became commercially available in other European countries. It was approved in the United States in 2008 and in many countries in 2009.
Structure and properties
Bendamustine (C16H21Cl2N3O2, Mr = 358.26 g/mol) is a derivative of chloromethine (mechlorethamine, nitrogen-lost). It has a similar structure to chlorambucil and cyclophosphamide, both of which are also used to treat chronic lymphocytic leukemia. However, it also has a benzimidazole group, such as cladribine, making it a purine analog as well. The 2-chloroethylamine group is responsible for the alkylating properties, and the butyric acid increases solubility. Bendamustine is present in drugs as a hydrochloride.
Effects
Bendamustine (ATC L01AA09) has antineoplastic properties by alkylating DNA, impairing DNA synthesis and repair, causing strand breaks, apoptosis, and cell death. As a purine analog, it may also be effective as an antimetabolite; however, this second mechanism is controversial. One advantage is low cross-resistance with other cytostatic drugs.
Indications
Bendamustine has been approved in many countries exclusively for the treatment of chronic lymphocytic leukemia. In other European countries, it is also approved for other malignancies, including Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, breast cancer, and multiple myeloma.
Dosage
According to the drug label. The drug is administered as a short-term infusion on days 1 and 2, with administration repeated every 4 weeks for multiple cycles. Dosage is based on body surface area.
Contraindications
Bendamustine should not be used in cases of hypersensitivity, during pregnancy or suspected pregnancy, during lactation, severe hepatic parenchymal damage, jaundice, existing severe bone marrow depression and severe blood count abnormalities, previous major surgical procedures, and infections, especially those associated with leukocytopenia. Full precautions can be found in the SmPC.
Interactions
Bendamustine is metabolized in the liver by CYP1A2, among others, and is conjugated with glutathione. The relevance of interactions via CYP1A2 is insufficiently studied; however, it should be combined with appropriate inhibitors or inducers only with caution. Other myelosuppressive agents may potentiate the effect on bone marrow.
Adverse effects
The most common adverse effects include infection, leukopenia, anemia, nausea and vomiting, mucosal inflammation, digestive symptoms such as diarrhea and constipation, and hypersensitivity reactions. Antiemetics are used to treat nausea and vomiting.
