- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Infusions containing bendamustine hydrochloride.
B-cell chronic lymphocytic leukaemia where fludarabine inappropriate
Combination treatment of multiple myeloma in patients over 65
Non-Hodgkin's lymphomas - secondary therapy
First-line treatment of chronic lymphocytic leukaemia (Binet stage B or C) in patients for whom fludarabine combination chemotherapy is not appropriate.
Indolent non-Hodgkin's lymphomas as monotherapy in patients who have progressed during or within 6 months following treatment with rituximab or a rituximab containing regimen.
Front line treatment of multiple myeloma (Durie-Salmon stage II with progress or stage III) in combination with prednisone for patients older than 65 years who are not eligible for autologous stem cell transplantation and who have clinical neuropathy at time of diagnosis precluding the use of thalidomide or bortezomib containing treatment.
Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.
Doses may vary significantly if this agent is used as monotherapy or different combinations.
When using this agent, specialist literature, national guidelines, cancer network protocols and Trust chemotherapy protocols should be consulted.
Monotherapy for Chronic Lymphocytic Leukaemia
100mg per metre squared of body surface area on days 1 and 2, every 4 weeks.
Monotherapy for Indolent Non-Hodgkin's Lymphomas Refractory to Rituximab
120mg per metre squared of body surface area on days 1 and 2, every 3 weeks.
120mg to 150mg per metre squared of body surface area on days 1 and 2, combined with 60mg of prednisone per metre squared of body surface area(given intravenously or orally) on days 1 to 4, every 4 weeks.
Patients with Hepatic Impairment
Severe hepatic impairment (serum bilirubin greater than 3mg/dl)
Moderate hepatic impairment (serum bilirubin between 1.2 and 3.0mg/dl)
30% dose reduction.
Mild hepatic impairment (serum bilirubin below 1.2mg/dl)
No dose adjustment.
Additional Dosage Information
Leukocyte count below 3 x 10 to the power of 9 per litre, or platelet count below 75 x 10 to the power of 9 per litre
Interrupt or discontinue treatment. Consider resuming treatment if leukocyte count recovers to greater than 4 x 10 to the power of 9 per litre, and platelet count recovers to 100 x 10 to the power of 9 per litre.
Non-haematological toxicity- based on worst grade experienced in previous cycle
Grade 3: 50% dose reduction, applied on day 1 and 2 of the respective treatment cycle.
Grade 4: Interrupt treatment.
For intravenous infusion over 30 to 60 minutes.
Children under 18 years
Leucocyte count below 3 x 10 to the power of 9 / L
Platelet count below 75 x 10 to the power of 9 / L
Within 30 days of major surgery
Severe hepatic impairment
Precautions and Warnings
Leucocyte count below 4 x 10 to the power of 9 / L
Platelet count below 100 x 10 to the power of 9/ L
Risk factors for skin cancer
History of cardiac disorder
History of hepatitis B
Moderate hepatic impairment - serum bilirubin between 1.2mg and 3mg/dl
Severe renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Anti-emetics may be required during therapy
Before initiating screen all patients for hepatitis B infection
CD4+ T-cell count below 200 per microlitre: Consider PJP prophylaxis
Consider premedication for patients with history of infusion reactions
Consider premedication with hypouricaemic agent
Give pre-treatment counselling and consideration of sperm cryopreservation
Hepatitis B: Refer prior to initiation to liver disease specialist
Maintain adequate hydration of patient prior / during treatment
Monitor patients for non-melanoma skin cancer prior to and during treatment
Consult local policy on the safe use of anti-cancer drugs
If extravasation occurs follow local policy & seek expert help immediately
Staff: Not to be handled by pregnant staff
Treatment to be administered by or under supervision of specialist
Consider PTLD or PML if new or worsening neurological symptoms occur
If rash develops, consider possibility of Stevens-Johnson Syndrome
Increase monitoring of ECG when serum potassium below 3.5mEq/l
Monitor ECG prior to and during treatment in existing cardiac abnormalities
Monitor for active hepatitis B during therapy and for several months after
Monitor full blood counts weekly
Monitor patient for infusion-associated reactions (IARs)
Monitor patients for signs of tumour lysis syndrome
Monitor respiratory function
Monitor serum potassium in patients with cardiac disorders
Monitor uric acid levels
Advise patient to report headaches, seizures, confusion, visual disturbance
Advise patient to report symptoms of infection immediately
May affect immune response to live vaccines
Potassium supplements may be required
Potentially mutagenic and carcinogenic
Reactivation of hepatitis B may occur in chronic carriers
Secondary tumours may occur as long-term sequelae
Discontinue if Progressive multifocal leukoencephalopathy (PML) develops
Discontinue if serious allergic or anaphylactic reaction occurs
Discontinue if severe skin reaction occurs
Discontinue treatment if progressive skin rash occurs
Suspend treatment if opportunistic infection is suspected
Interrupt treatment if grade 4 non-haematological toxicity occurs
Reduce dose if grade 3 non-haematological toxicity occurs
Female: Ensure adequate contraception during treatment
Male: Contraception required during and for 6 months after treatment
Advise patient to inform physician of any skin changes immediately
Patients with lymphocytopenia and low CD-4 positive T-cell counts have an increased susceptibility to opportunistic infections during and up to 9 months after discontinuing treatment, particularly in patients treated with concomitant rituximab.
Progressive Multifocal Leukoencephalopathy Syndrome (PML)
Progressive multifocal leukoencephalopathy syndrome (PML) has been reported in some patients treated with this agent, usually in combination with rituximab or obinutuzumab. If patients present with symptoms indicating PML such as worsening neurological, cognitive or behavioural signs or symptoms, an MRI should be performed. If PML is diagnosed, treatment should be permanently discontinued.
Patients treated with bendamustine hydrochloride may experience myelosuppression. In the event of treatment-related myelosuppression, leukocytes, platelets, haemoglobin, and neutrophils must be monitored at least weekly. Prior to the initiation of the next cycle of therapy, the following parameters are recommended: Leukocyte and/or platelet values greater than 4000 per microlitre or greater than 100,000 per microlitre respectively.
Pregnancy and Lactation
Bendamustine is contraindicated during pregnancy.
The manufacturer recommends that bendamustine should not be used during pregnancy unless clearly necessary. In non-clinical studies bendamustine was shown to be mutagenic and teratogenic. If the use of bendamustine is absolutely necessary during pregnancy or inadvertent pregnancy occurs during treatment, the woman should be advised of the possible risk for severe adverse effects in the embryo and fetus.
Bendamustine is contraindicated during breastfeeding.
Use of bendamustine when breastfeeding is contraindicated by the manufacturer. The manufacturer recommends that breastfeeding must be discontinued during bendamustine treatment. It is not known whether this agent or its metabolites are excreted in human breast milk. Effects on exposed infants are unknown.
The effect of concurrent therapies must also be considered.
Acute myeloid leukaemia
Blood urea increased
Bone marrow failure
Drug rash with eosinophilia and systemic symptoms (DRESS)
Increase in alkaline phosphatase
Increase in creatinine
Increase in serum ALT/AST
Pneumocystis jiroveci pneumonia
Progressive multifocal leukoencephalopathy (PML)
Reactivation of hepatitis B
Serum bilirubin increased
Toxic epidermal necrolysis
Tumour lysis syndrome
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Last Full Review Date: February 2019
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Summary of Product Characteristics: Bendamustine hydrochloride 25mg/ml concentrate for solution for infusion. Accord UK Ltd. February 2022.
Summary of Product Characteristics: Levact 2.5mg/ml powder for concentrate for solution for infusion. Napp Pharmaceuticals Ltd. January 2019.
Summary of Product Characteristics: Bendamustine powder for concentrate for solution for infusion. Actavis UK Ltd. February 2018.
Summary of Product Characteristics: Bendamustine hydrochloride 2.5mg/ml powder for concentrate for solution for infusion. Accord UK Ltd. December 2020.
Summary of Product Characteristics: Bendamustine hydrochloride 2.5mg/ml powder for concentrate for solution for infusion. Dr Reddy's UK Ltd. February 2019.
Summary of Product Characteristics: Bendamustine hydrochloride 180mg/4mg/ml powder for concentrate for solution for infusion. Dr Reddy's UK Ltd. February 2019.
HPRA Safety Notice June 2017
Last accessed: 25 August 2017.
MHRA Drug Safety Update July 2017
Available at: https://www.mhra.gov.uk
Last accessed: 25 August 2017.
MHRA Drug Safety Update March 2021 Available at: https://www.mhra.gov.uk
Last accessed: 16 March 2022.
NICE Evidence Services
Available at: www.nice.org.uk
Last accessed: 16 March 2022.
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Medscape UK | Univadis prescription drug monographs & interactions are based on FDB Multilex Content
FDB Disclaimer : FDB Multilex is intended for the use of healthcare professionals and is provided on the basis that the healthcare professionals will retain FULL and SOLE responsibility for deciding what treatment to prescribe or dispense for any particular patient or circumstance.