Overview
11 DESCRIPTION Bendamustine hydrochloride is an alkylating agent. The chemical name of bendamustine hydrochloride is 1H-benzimidazole-2-butanoic acid, 5-[bis(2-chloroethyl)amino]-1 methyl-, monohydrochloride, monohydrate. Its empirical molecular formula is C 16 H 21 Cl 2 N 3 O 2 · HCl. H 2 O, and the molecular weight is 412.74 g/mol.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Bendamustine is a bifunctional mechlorethamine derivative containing a purine-like benzimidazole ring. Mechlorethamine and its derivatives form electrophilic alkyl groups. These groups form covalent bonds with electron-rich nucleophilic moieties, resulting in interstrand DNA crosslinks. The bifunctional covalent linkage can lead to cell death via several pathways. Bendamustine is active against both quiescent and dividing cells. The exact mechanism of action of bendamustine remains unknown. 12.2 Pharmacodynamics Based on the pharmacokinetics/pharmacodynamics analyses of data from adult NHL patients, nausea increased with increasing bendamustine C max .
Indications
- 1 INDICATIONS AND USAGE Non-Hodgkin Lymphoma (NHL) Bendamustine hydrochloride injection is indicated for the treatment of adult patients with indolent B-cell non-Hodgkin lymphoma that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. Bendamustine hydrochloride injection is an alkylating drug indicated for treatment of adult patients with: • Indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. ( 1 )
Common Doses
- 120 mg
- 90 mg
- 60 mg
- 25 mg
Dosage
2 DOSAGE AND ADMINISTRATION For NHL : • 120 mg/m 2 infused intravenously over 60 minutes on Days 1 and 2 of a 21-day cycle, up to 8 cycles ( 2.1 ) 2.1 Dosing Instructions for NHL Recommended Dosage: The recommended dosage is 120 mg/m 2 administered intravenously over 60 minutes on Days 1 and 2 of a 21-day cycle, up to 8 cycles. Dose Delays, Dosage Modifications and Reinitiation of Therapy for NHL: Delay bendamustine hydrochloride injection administration in the event of a Grade 4 hematologic toxicity or clinically significant greater or equal to Grade 2 non-hematologic toxicity.
Contraindications
- 4 CONTRAINDICATIONS Bendamustine hydrochloride injection is contraindicated in patients with a known hypersensitivity (e.g., anaphylactic and anaphylactoid reactions) to bendamustine, polyethylene glycol 400, absolute ethanol, sodium hydroxide and monothioglycerol. [see Warnings and Precautions ( 5.4 )] Bendamustine hydrochloride injection is contraindicated in patients with a history of a hypersensitivity reaction to bendamustine, polyethylene glycol 400, absolute ethanol, sodium hydroxide and monothioglycerol.
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant serious adverse reactions are discussed in greater detail in other sections of the prescribing information. Myelosuppression [see Warnings and Precautions ( 5.1 )] Infections [see Warnings and Precautions ( 5.2 )] Progressive Multifocal Leukoencephalopathy [see Warnings and Precautions ( 5.3 )] Anaphylaxis and Infusion Reactions [see Warnings and Precautions ( 5.4 )] Tumor Lysis Syndrome [see Warnings and Precautions ( 5.5 )] Skin Reactions [see Warnings and Precautions ( 5.6 )] Hepatotoxicity [see Warnings and Precautions ( 5.
Interactions
- 7 DRUG INTERACTIONS Consider alternative therapies that are not CYP1A2 inducers or inhibitors during treatment with bendamustine hydrochloride injection. ( 7.1 ) 7.1 Effect of Other Drugs on Bendamustine Hydrochloride Injection CYP1A2 Inhibitors The coadministration of bendamustine hydrochloride injection with CYP1A2 inhibitors may increase bendamustine plasma concentrations and may result in increased incidence of adverse reactions with bendamustine hydrochloride injection [see Clinical Pharmacology ( 12.3 )].