Bendamustine

Registered South African indications:

• Chronic lymphocytic leukaemia
• Non-Hodgkin’s lymphoma
• Multiple myeloma

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Breastfeeding
• Severe hepatic impairment
• Jaundice
• Severe bone marrow suppression
• Severe blood count alterations
• Major surgery within 30 days of start of treatment
• Infections
• Yellow fever vaccination

Cautions

• End-stage renal impairment
• Moderate hepatic impairment
• Chronic carriers of hepatitis B
• Cardiac disorders
• Men and women of child bearing potential

Forms avail. in SA and covered in this monograph: inj

Used for the treatment of

Chronic lymphocytic leukaemia
- First line treatment in patients whom fludarabine combination therapy is not appropriate
Non-Hodgkin’s lymphoma 
- First line treatment of indolent CD4 20 positive non-Hodgkin's lymphoma (additional agent required)
- 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
Multiple myeloma (additional agent required)
- For patients older than 65 years who are not eligible for autologous stem cell transplantation and who have clinical neuropathy at the time of diagnosis 

Consult specialist for dosages and regimens

Not established for use in children

Pregnancy

• Caution; positive evidence of risk
• There are insufficient data from the use of bendamustine in pregnant women. In nonclinical studies, bendamustine hydrochloride was embryo-/fetolethal, teratogenic and genotoxic.
• During pregnancy, bendamustine should not be used unless clearly necessary. The mother should be informed about the risk to the foetus. If treatment with bendamustine is absolutely necessary during pregnancy or if pregnancy occurs during treatment, the patient should be informed about the risks for the unborn child and be monitored carefully. The possibility of genetic counselling should be considered
• Women of childbearing potential must use effective methods of contraception both before and during bendamustine therapy.
  Men being treated with bendamustine are advised not to father a child during and for up to 6 months following cessation of treatment. Advice on conservation of sperm should be sought prior to treatment because of the possibility of irreversible infertility due to therapy with bendamustine

Breastfeeding

• Contraindicated
• It is not known whether bendamustine passes into the breast milk, therefore, bendamustine is contraindicated during breastfeeding. Breastfeeding must be discontinued during treatment with bendamustine

Renal Impairment

• Caution; dose adjustment recommended
• Consult Oncology specialist for any possible dose adjustments and regimens

Hepatic Impairment

• Consult Oncology specialist for any possible dose adjustments and regimens
• Mild (Child-Pugh Class A): No dose adjustment recommended
• Moderate (Child-Pugh Class B): Use with caution. Closely monitor liver function (ALT, AST and total bilirubin). If ALT/AST increased by more than 205-times ULN, and/or total bilirubin increased by more than 1.5-times ULN = Discontinue  
• Severe (Child-Pugh Class C): Contraindicated

Elderly

• No dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Insomnia
• Dizziness
• Somnolence
• Aphonia
• Dysgeusia
• Paraesthesia
• Peripheral sensory neuropathy
• Anticholinergic syndrome
• Neurological disorders
• Ataxia
• Encephalitis
• Fatigue

Cardiovascular Disorders

• Cardiac dysfunction
• Palpitations
• Angina pectoris
• Arrhythmia
• Pericardial effusion
• Tachycardia
• Myocardial infarction
• Cardiac failure
• Atrial fibrillation
• Hypotension
• Hypertension
• Acute circulatory failure
• Phlebitis

Respiratory Disorders

• Pulmonary dysfunction
• Pulmonary fibrosis
• Pneumocystis jirovecii pneumonia
• Atypical pneumonia

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Constipation
• Stomatitis
• Haemorrhagic oesophagitis
• Gastrointestinal haemorrhage

Hepatobiliary Disorders

• Increased aspartate aminotransferase
• Increase alanine aminotransferase
• Increased alkaline phosphatase 
• Increase bilirubin 

Genitourinary Disorders

• Amenorrhea
• Infertility
• Renal failure
• Increase creatinine 
• Increased urea

Endocrine and Metabolic Disorders

• Hypokalemia
• Dehydration
• Anorexia

Skin and Subcutaneous Tissue Disorders

• Alopecia
• Skin disorders 
• Erythema
• Dermatitis
• Pruritus
• Macular-papular rash
• Hyperhidrosis
• Stevens–Johnson syndrome
• Toxic epidermal necrolysis 

Immune, Blood and Lymphatic System Disorders

• Leukopenia 
• Thrombocytopenia
• Haemorrhage
• Anaemia
• Neutropenia
• Pancytopenia
• Bone marrow failure
• Haemolysis
• Hypersensitivity 
• Anaphylactic reaction
• Anaphylactoid reaction
• Anaphylactic shock
• Tumour lysis syndrome
• Myelodysplastic syndrome
• Acute myeloid leukemia
• Decreased haemoglobin 
• Mucosal inflammation
• Pyrexia
• Multi organ failure
• Opportunistic infection 
• Sepsis

• Myelosuppressive agents
• Ciclosporin 
• Tacrolimus 
• Live-virus vaccination
• CYP1A2 inhibitors

• Full blood count with differential
• Serum potassium
• Uric acid levels
• Renal function
• Hepatic function

Specific cases may require

• ECG

Bendamustine hydrochloride is an alkylating antitumour agent. The antineoplastic and cytocidal effect of bendamustine hydrochloride is based essentially on a cross linking of DNA single and double strands by alkylation. As a result, DNA matrix functions and DNA synthesis and repair are impaired.

Injection (per vial) 25mg

• Ribomustin (Astellas) originator

Injection (per vial) 100mg

• Ribomustin (Astellas) originator