Bendamustine

Bendamustine is a bifunctional mechlorethamine derivative capable of forming electrophilic alkyl groups that covalently bond to other molecules. Through this function as an alkylating agent, bendamustine causes intra- and inter-strand crosslinks between DNA bases resulting in cell death. It is active against both active and quiescent cells, although the exact mechanism of action is unknown.

Chronic lymphocytic leukaemia: 100 mg/m² infused over 30-60 min on days 1 and 2 of a 28-day cycle for up to 6 cycles. For severe haematological or non-haematological toxicity: Reduce dose to 50 mg/m² on days 1 and 2 of each cycle. If severe haematological toxicity recurs, further reduce dose to 25 mg/m² on days 1 and 2 of each cycle. May consider dose re-escalation in subsequent cycles.

Multiple myeloma: 120-150 mg/m² infused over 30-60 min on days 1 and 2 of a 28-day cycle. IV or oral prednisone may be given at a dose of 60 mg/m² on days 1-4 of the cycle.

Non-Hodgkin's lymphoma: 120 mg/m² infused over 30-60 min on days 1 and 2 of a 21-day cycle for up to 8 cycles. For severe haematological or non-haematological toxicity: Reduced to 90 mg/m² on days 1 and 2 of each cycle. If severe toxicity recurs, further reduce dose to 60 mg/m² on days 1 and 2 of each cycle.

May increase plasma levels with CYP1A2 inhibitors (e.g. ciprofloxacin, fluvoxamine). May reduce plasma levels with CYP1A2 inducers (e.g. omeprazole and tobacco smoking).

Patient with history of hypersensitivity (e.g. anaphylaxis and anaphylactoid reactions); jaundice, severe bone marrow suppression, low leukocyte or platelet count. Severe hepatic impairment. Major surgery <30 days prior to treatment.

Malignant and pre-malignant disease; pyrexia, nausea, vomiting, cough, headache, fatigue, diarrhoea, constipation, anorexia, wt decrease, rash, stomatitis, lymphopenia, anaemia, thrombocytopenia, leucopenia, neutropenia.

Pregnancy category D. There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Mild to moderate hepatic and renal impairment. Pregnancy and lactation.

Hepatic Impairment: Moderate: Reduce dose by 30%.

Symptoms: Cardiotoxicity, thrombocytopenia.

Management: May perform bone marrow transplantation and transfusions to control haematological effects. It is dialysable to a small extent.

Cytotoxic Chemotherapy

Reconstitute powder for inj by adding 5 ml or 20 ml of sterile water for inj to a vial containing 25 mg or 100 mg, respectively to provide a soln containing 5 mg/ml. The lyophilised powder should be dissolved w/in 5 min, shake well to facilitate dissolution. within 30 min of reconstitution, the appropriate volume should be withdrawn from the vial to further dilute in 500 ml of either NaCl 0.9% inj or dextrose 2.5% and NaCl 0.45% inj to a final concentration of 0.2-0.6 mg/ml.

Store below 25° C, prior to reconstitution. Protect from light.