Bendamustine for Injection is indicated for treatment of patients with:

• Chronic lymphocytic leukemia (CLL).
• Indolent B-cell non-Hodgkin’s lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab containing regimen.

Chronic Lymphocytic Leukemia(CLL)

Non-Hodgkin's Lymphoma

For Chronic Lymphocytic Leukemia:

• 100 mg/m² infused intravenously over 30 minutes on Days 1 and 2 of a 28 day cycle, up to 6 cycles
• Dose modifications for hematologic toxicity: for Grade 3 or greater toxicity, reduce dose to 50 mg/m² on Days 1 and 2; if Grade 3 or greater toxicity recurs, reduce dose to 25 mg/m2 on Days 1 and 2. 
• Dose modifications for non-hematologic toxicity: for clinically significant Grade 3 or greater toxicity, reduce the dose to 50 mg/m² on Days 1 and 2 of each cycle. 
• Dose re-escalation may be considered. 

For Non Hodgkin's Lymphoma:

• 120 mg/m² infused intravenously over 60 minutes on Days 1 and 2 of a 21 day cycle, up to 8 cycles
• Dose modifications for hematologic toxicity: for Grade 4 toxicity, reduce the dose to 90 mg/m2 on Days 1 and 2 of each cycle; if Grade 4 toxicity recurs, reduce the dose to 60 mg/m² on Days 1 and 2 of each cycle.
• Dose modifications for non-hematologic toxicity: for Grade 3 or greater toxicity, reduce the dose to 90 mg/m² on Days 1 and 2 of each cycle; if Grade 3 or greater toxicity recurs, reduce the dose to 60 mg/m2 on Days 1 and 2 of each cycle. 

General Dosing Considerations: 

• Delay treatment for Grade 4 hematologic toxicity or clinically significant ≥ Grade 2 non-hematologic toxicity.
• Bendamustine for Injection must be reconstituted and further diluted prior to infusion.

Most common non-hematologic adverse reactions for CLL:

• fever
• nausea
• vomiting

Most common non-hematologic adverse reactions for NHL:

• nausea
• fatigue
• vomiting
• diarrhea
• pyrexia
• constipation
• anorexia
• cough
• headache
• weight loss
• dyspnea
• rash
• stomatitis

Fever	Nausea	Constipation
Anorexia	Coughing	Headache

• Myelosuppression: Treatment should be postponed or dose reduced if necessary. Based on absolute neutrophil count and platelet count recovery, closely monitor and restart treatment. Myelosuppression complications can be fatal.
• Infections:  Patient should be observed for fever and other signs of infection and should be treated promptly.
• Infusion Reactions and Anaphylaxis: Anaphylactic reactions have been severe. If there are severe reactions, the drug should be discontinued. Inquire with patients about their reactions following the first cycle. Consider pre-treatment for subsequent cycles after milder reactions.
• Tumor Lysis Syndrome: Acute renal failure and death are possible outcomes. Precautions should be taken in patients who are at high risk.
• Discontinue for severe skin reactions: In the event of severe skin reactions, discontinue use.
• Use in Pregnancy:  Fetal harm can occur when administered to a pregnant woman. Women should be advised to avoid becoming pregnant when receiving Bendamustine.