Bendamustine Hydrochloride (5 brand names, 3 dosage forms, 3 routes)
Available dosage forms: POWDER, SOLUTION, INJECTABLE.
Routes of administration: INTRAVENOUS, IV (INFUSION), INJECTION.
Brand Names
- BELRAPZO
- BENDAMUSTINE HYDROCHLORIDE
- BENDEKA
- TREANDA
- VIVIMUSTA
Contraindications
Bendamustine Hydrochloride Injection is contraindicated in patients with a known hypersensitivity (e.g., anaphylactic and anaphylactoid reactions) to bendamustine, polyethylene glycol 400, polyethylene glycol 300, or butylated hydroxytoluene. [see Warnings and Precautions (5.4)]
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 (5.7)] Other Malignancies [see Warnings and Precautions (5.8)] Extravasation Injury [see Warnings and Precautions (5.9)]
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.
Overdosage
The intravenous LD50 of bendamustine hydrochloride is 240 mg/m2 in the mouse and rat. Toxicities included sedation, tremor, ataxia, convulsions and respiratory distress. Across all clinical experience, the reported maximum single dose received was 280 mg/m2. Three of four patients treated at this dose showed ECG changes considered dose-limiting at 7 and 21 days post-dosing. These changes included QT prolongation (one patient), sinus tachycardia (one patient), ST and T wave deviations (two patients) and left anterior fascicular block (one patient). Cardiac enzymes and ejection fractions remained normal in all patients. No specific antidote for bendamustine hydrochloride overdose is known. Management of overdosage should include general supportive measures, including monitoring of hematologic parameters and ECGs.