bendamustine hydrochloride monohydrate: clinical use

Prescribing considerations

• Treatment requires supervision by a clinician experienced in chemotherapy.
• Assess marrow reserve, active infection, hepatic function, recent surgery, cardiac history, pregnancy potential and concomitant immunosuppression.
• Screen for hepatitis B before treatment; obtain specialist input and monitor carriers for reactivation.
• Assess tumour-lysis risk and use hydration, biochemical monitoring and preventive treatment where appropriate.
• Consider prolonged lymphopenia, CD4 depletion and opportunistic-infection risk; PJP prophylaxis may be appropriate with low CD4 counts.
• Arrange periodic skin examination and investigate new neurological, cognitive or behavioural symptoms for possible PML.
• Ensure the transfusion service knows the patient has received bendamustine because irradiated cellular blood components may be required.

Contraindications and cautions

• Hypersensitivity to bendamustine or an excipient
• Breastfeeding
• Severe hepatic impairment or jaundice
• Severe bone-marrow suppression or severe blood-count abnormalities
• Recent major surgery
• Infection, particularly with leucopenia
• Yellow fever vaccination

Monitoring

• Full blood count, including neutrophils and platelets
• Clinical signs of bacterial, viral and opportunistic infection
• Lymphocyte and CD4 counts where clinically indicated
• Hepatitis B status and reactivation risk
• Renal function, uric acid and electrolytes during tumour-lysis risk
• Liver function
• Potassium and ECG in patients with cardiac disease
• Infusion reactions and extravasation
• Skin changes and new neurological symptoms

Clinical pharmacology

Bendamustine is an alkylating antineoplastic agent that cross-links DNA, impairing DNA function, synthesis and repair. Clearance includes hydrolysis, glutathione conjugation and partial CYP1A2-mediated hepatic metabolism; plasma-protein binding is high.

Formulation and product differences

• Both selected products are powders requiring reconstitution with water for injections and dilution only with sodium chloride solution before intravenous infusion.
• The Seacross formulation lists mannitol and hydrochloric acid for pH adjustment; the selected Zentiva formulation lists mannitol.

Solution for infusion

Route: Intravenous

Strengths: 2.5 mg/mL, 180 mg/4 mL