Bendamax

Chronic lymphocytic leukaemia, Non-hodgkin's lymphoma, Multiple myeloma

Intravenous Chronic lymphocytic leukaemia Adult: 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 Adult: 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 Adult: 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. Hepatic Impairment Mild: Use caution Moderate: Reduce dose by 30%. Severe hepatic impairment: Use not recommended

Renal Impairment Mild-to-moderate: Use caution CrCl <40 mL/min: Not recommended

Patient w/ 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.

Bendamustine is an antineoplastic alkylating agent. It interferes w/ DNA replication and RNA transcription that leads to disruption of nucleic acid function. It is also active against inert and dividing cells.

Interrupt if severe infusion reactions Mild-mod renal impairment, mild hepatic impairment Possibility of anaphylactic/infusion reactions: severe in rare cases Myelosuppression may occur; delay or reduce dose; restart treatment based on ANC and platelet count recovery; complications of myelosuppression may lead to death Monitor for fever and other signs of infection and treat promptly Severe infusion and anaphylactic reactions reported; monitor clinically and discontinue therapy; premedicate in subsequent cycles for milder reactions Tumor lysis syndrome reported; acute renal failure and death may occur; anticipate and use supportive measures Discontinue for severe skin reactions; cases of SJS and TEN, some fatal, reported when bendamustine was administered concomitantly with allopurinol and other medications known to cause these syndromes Premalignant and malignant diseases reported Erythema and maked swelling can occur with extravasation; assure good venous access and monitor infusion site during and after administration Fetal harm can occur when administered to a pregnant woman; women should be advised to avoid becoming pregnant when receiving bendamustine Increased risk for reactivation of infections including (but not limited to) hepatitis B, cytomegalovirus, Mycobacterium tuberculosis, and herpes zoster; patients should undergo appropriate measures (including clinical and laboratory monitoring, prophylaxis, and treatment) for infection and infection reactivation prior to administration Lactation: It is not known whether this drug is excreted in milk. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

>10% Lymphopenia (68-99%),Leukopenia (61-94%; grade 3/4, 28-56%),Anemia (88-89%; grades 3/4 11-13%),Thrombocytopenia (77-86%; grade 3/4, 11-25%),,Neutropenia (75-86%; grade 3/4, 43-60%),Nausea (20-75%),Fatigue (9-57%),Vomiting (16-40%),Diarrhea (9-37%),Bilirubin increased (<34%; grade 3/4, 3%),Constipation (<29%),Fever (24-34%),Pyrexia (24%),Anorexia (<23%),Cough (4-22%)Headache (<21%),Weight loss (7-18%),Dehydration (<16%),Rash (8-16%),Stomatitis (<15%),Back pain (<14%),Dizziness (<14%),Chills (6-14%),Peripheral edema (13%),Abdominal pain (5-13%),Insomnia (<13%),Dyspepsia (<11%),Weakness (8-11%) 1-10% Upper respiratory infection (10%),Gastroesophageal reflux disease (<10%),Urinary tract infection (<10%),Xerostomia (9%),Hypokalemia (<9%),Anxiety (8%),Hyperuricemia (<7%),Tachycardia (<7%),Taste alteration (<7%),Arthralgia (<6%),Chest pain (<6%),Depression (<6%),Hypotension (<6%),Injection site pain (<6%),Pain (<6%),Pruritus (5-6%),Febrile neutropenia (3-6%),Rash (5%) Potentially Fatal: Myelosuppression, tumour lysis syndrome which may lead to acute renal failure, infections (e.g. sepsis, pneumonia, septic shock), Stevens-Johnson syndrome, toxic epidermal necrolysis. Rarely, severe anaphylatic and anaphylactoid reactions.

Pregnancy There are no available data on use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes; advise pregnant women of potential risk to fetus Pregnancy testing recommended for females of reproductive potential prior to initiation of therapy Contraception Therapy can cause embryo-fetal harm when administered to pregnant women; advise female patients of reproductive potential to use effective contraception during treatment and for 6 months after final dose Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with drug and for at least 3 months after final dose Infertility Based on findings from clinical studies, therapy may impair male fertility; impaired spermatogenesis, azoospermia, and total germinal aplasia have been reported in male patients treated with alkylating agents, especially in combination with other drugs; in some instances spermatogenesis may return in patients in remission, but this may occur only several years after intensive chemotherapy has been discontinued; advise patients of potential risk to their reproductive capacities Based on findings from animal studies, drug may impair male fertility due to an increase in morphologically abnormal Spermatozoa; the long-term effects of therapy on male fertility, including the reversibility of adverse effects, have not been studied Animal data In animal reproduction studies, intraperitoneal administration to pregnant mice and rats during organogenesis at doses 0.6-1.8 times the maximum recommended human dose (MRHD) resulted in embryo-fetal and/or infant mortality, structural abnormalities, and alterations to growth Lactation There are no data on presence of drug or metabolites in either human or animal milk, effects on breastfed child, or on milk production; because of potential for serious adverse reactions in breastfed child, advise patients that breastfeeding is not recommended during treatment and for at least 1 week after the last dose

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