Adult: In patients with indolent B-cell non-Hodgkin's lymphoma that progressed during or within 6 months of rituximab treatment or a rituximab-containing regimen: 120 mg/m2 via infusion over 30-60 minutes on days 1 and 2 of a 21-day cycle for up to 8 cycles. For severe haematological or non-haematological toxicity: Reduce dose to 90 mg/m2 on days 1 and 2 of each cycle. For recurrent severe haematological or non-haematological toxicity: Further reduce the dose to 60 mg/m2 on days 1 and 2 of each cycle. Dosing interruption or discontinuation may be required according to individual safety or tolerability. Treatment or dosing recommendations may vary among individual products and between countries. Refer to detailed product or local treatment guidelines.
Intravenous Chronic lymphocytic leukaemia
Adult: 100 mg/m2 via infusion over 30-60 minutes 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. For recurrent severe haematological toxicity: further reduce dose to 25 mg/m2 on days 1 and 2 of each cycle. Dosing interruption or discontinuation may be required according to individual safety or tolerability. Treatment or dosing recommendations may vary among individual products and between countries. Refer to detailed product or local treatment guidelines.
Hepatic Impairment
Moderate: Reduce dose by 30%. Severe: Contraindicated.
Reconstitution
Dilute with the appropriate amount of infusion solution to prepare the recommended concentration. Instructions for reconstitution may vary among individual products and between countries (refer to specific product guidelines).
Contraindications
Hypersensitivity. Severe bone marrow suppression or low leukocyte or platelet count; infections (involving leukocytopenia); jaundice. Severe hepatic impairment. Lactation. Concomitant yellow fever vaccine administration.
Special Precautions
Patient with myelosuppression (e.g. with lymphopenia or low CD4-positive T-cell count) and current or history of cardiac disease. Defer treatment for at least 30 days after major surgery. Renal and moderate hepatic impairment. Pregnancy.
Adverse Reactions
Significant: Bone marrow suppression (e.g. leucopenia, thrombocytopenia, anaemia); opportunistic infections (e.g. Pneumocystis jirovecii pneumonia, cytomegalovirus, herpes zoster); secondary malignancies (e.g. acute myeloid leukaemia, bronchial carcinoma, myelodysplastic syndrome, myeloproliferative disorders, non-melanoma skin cancer [e.g. basal or squamous cell carcinoma]); extravasation. Cardiac disorders: Angina pectoris, arrhythmia, palpitations, tachycardia. Gastrointestinal disorders: Nausea, vomiting, dry mouth, dysgeusia, diarrhoea, constipation, abdominal pain or distention, dyspepsia, stomatitis, GERD. General disorders and administration site conditions: Pyrexia, chills, fatigue, asthenia, dehydration, pain, mucosal inflammation, peripheral oedema; infusion site reactions (e.g. pain, erythema, inflammation). Hepatobiliary disorders: Hepatitis. Infections and infestations: Oral candidiasis, UTI, URTI. Investigations: Decreased weight; increased creatinine, urea, ALT, AST, bilirubin, alkaline phosphatase. Metabolism and nutrition disorders: Anorexia, decreased appetite, hypokalaemia, hyperuricaemia. Musculoskeletal and connective tissue disorders: Back pain, chest pain, limb pain, arthralgia, ostealgia. Nervous system disorders: Headache, somnolence. Psychiatric disorders: Insomnia, anxiety, depression. Reproductive system and breast disorders: Amenorrhoea. Respiratory, thoracic and mediastinal disorders: Cough, wheezing, dyspnea, nasal congestion, nasopharyngitis, sinusitis, pharyngeal pain. Skin and subcutaneous tissue disorders: Rash, urticaria, alopecia, hyperhidrosis, night sweats. Vascular disorders: Hypotension, hypertension, haemorrhage. Potentially Fatal: Severe thrombocytopenia, febrile neutropenia; sepsis, shock, pneumonia, progressive multifocal leukoencephalopathy; severe skin reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, bullous exanthema); cardiac failure and MI; tumour lysis syndrome (may lead to acute renal failure); hepatotoxicity, HBV reactivation. Rarely, anaphylaxis or anaphylactoid reactions.
Women of childbearing potential must use proven birth control methods during therapy and for 6 months after the last dose. Males with female partners of childbearing potential must also use effective contraception during treatment and for 6 months after the last dose. This drug may occasionally cause somnolence, if affected, do not drive or operate machinery.
Monitoring Parameters
Screen for pregnancy status in females of childbearing potential before treatment initiation. Monitor CBC with differential and platelet count; serum creatinine; LFTs (e.g. AST, ALT, total bilirubin) before and during treatment; serum K and uric acid levels (patient at risk for tumour lysis syndrome); IV site during and after infusion. Conduct HBV screening including HBsAg, HBV core antibody, total Ig or IgG, and antibody to HBV surface antigen before (or at the beginning of) systemic chemotherapy. Assess for signs and symptoms of infusion reactions, anaphylaxis, severe skin reactions, infections, progressive multifocal leukoencephalopathy, tumor lysis syndrome; development of secondary malignancies.
Overdosage
Symptoms: Grade 4 thrombocytopenia and ECG changes (e.g. left anterior fascicular block, prolonged QT, ST and T wave displacement, sinus tachycardia). Management: Supportive treatment. To manage haematological adverse effects, consider bone marrow transplantation, initiate blood transfusions, or administer haematological growth factors. Closely monitor patient's ECG and haematological parameters.
Drug Interactions
Increased plasma concentration with CYP1A2 inhibitors (e.g. acyclovir, ciprofloxacin, cimetidine, fluvoxamine). Reduced plasma concentration with CYP1A2 inducers. Enhanced immunosuppression with ciclosporin and tacrolimus. Potentially Fatal: Increased risk of infection with live-virus vaccines.
Action
Description: Mechanism of Action: Bendamustine, an antineoplastic agent, is an alkylating agent with a purine-like benzimidazole ring that is active against both dormant and dividing cells. It causes cell death via single and double-strand DNA cross-linking, thereby causing impaired DNA synthesis, repair, and matrix functions. Pharmacokinetics: Distribution: Distributed freely into human RBC. Plasma protein binding: Approx 95%, mainly to albumin. Metabolism: Extensively metabolised in the liver via hydrolysis into monohydroxy-bendamustine (HP1) and dihydroxy-bendamustine (HP2) as metabolites with low cytotoxic activity; and at a lesser extent by CYP1A2 isoenzyme to γ-hydroxyl-bendamustine (M3) and N-desmethyl-bendamustine (M4) as active minor metabolites. Excretion: Via urine (approx 50%; approx 3% as unchanged drug); faeces (approx 25%). Elimination half-life: Approx 40 minutes (bendamustine); approx 3 hours (M3); approx 30 minutes (M4).
Chemical Structure
Bendamustine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 65628, Bendamustine. https://pubchem.ncbi.nlm.nih.gov/compound/Bendamustine. Accessed Mar. 22, 2024.
Storage
Intact vials: Store below 30°C. Protect from light. Diluted solutions for IV infusion: Store between 2-8°C for 2 days or at 25°C for 3.5 hours. This is a cytotoxic drug, follow applicable procedures for receiving, handling, administration, and disposal. Storage recommendations may vary among individual products and between countries (refer to specific product guidelines).
L01AA09 - bendamustine ; Belongs to the class of alkylating agents, nitrogen mustard analogues. Used in the treatment of cancer.
References
Anon. Bendamustine Hydrochloride. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 06/02/2024.Anon. Bendamustine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 06/02/2024.Belrapzo Injection (Eagle Pharmaceuticals, Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/02/2024.Bendamustine Hydrochloride 25 mg/mL Concentrate for Solution for Infusion (Accord Healthcare Limited). MHRA. https://products.mhra.gov.uk. Accessed 06/02/2024.Bendeka Injection, Solution (Teva Pharmaceuticals USA, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/02/2024.Buckingham R (ed). Bendamustine Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/02/2024.Janssen-Cilag (New Zealand) Ltd. Ribomustin 25 mg and 100 mg Powder for Infusion data sheet 12 August 2022. Medsafe. http://www.medsafe.govt.nz. Accessed 06/02/2024.Joint Formulary Committee. Bendamustine Hydrochloride. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/02/2024.Ribomustin 25 mg/vial and 100 mg/vial Powder for Concentrate for Solution for Infusion (Johnson & Johnson Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 06/02/2024.Treanda Injection, Solution, Concentrate and Powder, Lyophilized, for Solution (Cehpalon, LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/02/2024.
Sign Out
