Bendeka (bendamustine) for Leukemia: Side Effects & Warnings

Generic drug: bendamustine hydrochloride

Brand name: Bendeka

What is Bendeka (bendamustine hydrochloride), and how does it work?

Bendeka (bendamustine hydrochloride) Injection is an alkylating drug indicated for treatment of patients with chronic lymphocytic leukemia (CLL), and indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.

What are the side effects of Bendeka?

Common side effects of Bendeka include:

• nausea,
• vomiting,
• fatigue,
• weakness,
• fever,
• diarrhea,
• constipation,
• anorexia,
• cough,
• headache,
• weight loss,
• shortness of breath,
• chills,
• pneumonia,
• drowsiness,
• rash,
• itching,
• inflammation of the mouth and lips,
• feeling unwell (malaise),
• dry mouth,
• runny or stuffy nose,
• weight loss,
• low levels of a type of white blood cell called lymphocytes in the blood (lymphopenia),
• low levels of iron in the blood (anemia),
• low levels of white blood cells (leukopenia),
• low levels of platelets in the blood (thrombocytopenia), and
• low levels of a type of white blood cell called neutrophils in the blood (neutropenia).

What is the dosage for Bendeka?

Dosing Instructions For CLL

Recommended Dosage

The recommended dose is 100 mg/m² administered intravenously over 10 minutes on Days 1 and 2 of a 28-day cycle, up to 6 cycles.

Dose Delays, Dose Modifications And Reinitiation Of Therapy For CLL

• Delay Bendeka administration in the event of Grade 4 hematologic toxicity or clinically significant greater than or equal to Grade 2 non-hematologic toxicity. Once non-hematologic toxicity has recovered to less than or equal to Grade 1 and/or the blood counts have improved [Absolute Neutrophil Count (ANC) greater than or equal to 1 x 10⁹/L, platelets greater than or equal to 75 x 10⁹/L], reinitiate
  Bendeka (bendamustine hydrochloride) injection at the discretion of the
  treating physician. In addition, consider dose reduction.
• Dose modifications for hematologic toxicity: for Grade 3 or greater toxicity, reduce the dose to 50 mg/m² on Days 1 and 2 of each cycle; if Grade 3 or greater toxicity recurs, reduce the dose to 25 mg/m² on Days 1 and 2 of each cycle.
• 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.
• Consider dose re-escalation in subsequent cycles at the discretion of the treating physician.

Dosing Instructions For NHL

Recommended Dosage

The recommended dose is 120 mg/m² administered intravenously over 10 minutes on Days 1 and 2 of a 21-day cycle, up to 8 cycles.

Dose Delays, Dose Modifications And Reinitiation Of Therapy For NHL

• Delay Bendeka administration in the event of a Grade 4 hematologic toxicity or clinically significant greater than or equal to Grade 2 non-hematologic toxicity. Once non-hematologic toxicity has recovered to less than or equal to Grade 1 and/or the blood counts have improved [Absolute Neutrophil Count (ANC) greater than or equal to 1 x 10⁹/L, platelets greater than or equal to 75 x 10⁹/L], reinitiate
  Bendeka at the discretion of the treating physician. In addition, consider
  dose reduction.
• 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.

Preparation For Intravenous Administration

• Bendeka is a cytotoxic drug. Follow applicable special handling and disposal procedures.¹
• Bendeka is in a multiple-dose vial. At room temperature, Bendeka is a clear, and colorless to yellow ready-to-dilute solution.
• Store Bendeka at recommended refrigerated storage conditions (2-8°C or 36-46°F).
• When refrigerated, the contents may freeze.
• Allow the vial to reach room temperature (15-30°C or 59-86°F) prior to use.
• Do not use the product if particulate matter is observed after achieving room temperature.

Intravenous Infusion

• Aseptically withdraw the volume needed for the required dose from the 25 mg/mL solution as per Table A below and immediately transfer the solution to a 50 mL infusion bag of one of the following diluents:
  • 0.9% Sodium Chloride Injection, USP; or
  • 2.5% Dextrose/0.45% Sodium Chloride Injection, USP; or
  • 5% Dextrose Injection, USP.

The resulting final concentration of bendamustine hydrochloride in the infusion bag should be within 1.85 mg/mL – 5.6 mg/mL. After transferring, thoroughly mix the contents of the infusion bag. The admixture should be a clear, and colorless to yellow solution.

No other diluents have been shown to be compatible. The 5% Dextrose Injection, USP, offers a sodium-free method of administration for patients with certain medical conditions requiring restricted sodium intake.

Table A: Volume (mL) of Bendeka required for dilution into 50 mL of 0.9% saline, or 0.45% saline/2.5% dextrose or 5% dextrose for a given dose (mg/m²) and Body Surface Area (m²)

Body Surface Area (m²)
Volume of Bendeka to withdraw (mL)

120 mg/m²
100 mg/m²
90 mg/m²
60 mg/m²
50 mg/m²
25 mg/m²

1
4.8
4
3.6
2.4
2
1

1.1
5.3
4.4
4
2.6
2.2
1.1

1.2
5.8
4.8
4.3
2.9
2.4
1.2

1.3
6.2
5.2
4.7
3.1
2.6
1.3

1.4
6.7
5.6
5
3.4
2.8
1.4

1.5
7.2
6
5.4
3.6
3
1.5

1.6
7.7
6.4
5.8
3.8
3.2
1.6

1.7
8.2
6.8
6.1
4.1
3.4
1.7

1.8
8.6
7.2
6.5
4.3
3.6
1.8

1.9
9.1
7.6
6.8
4.6
3.8
1.9

2
9.6
8
7.2
4.8
4
2

2.1
10.1
8.4
7.6
5
4.2
2.1

2.2
10.6
8.8
7.9
5.3
4.4
2.2

2.3
11
9.2
8.3
5.5
4.6
2.3

2.4
11.5
9.6
8.6
5.8
4.8
2.4

2.5
12
10
9
6
5
2.5

2.6
12.5
10.4
9.4
6.2
5.2
2.6

2.7
13
10.8
9.7
6.5
5.4
2.7

2.8
13.4
11.2
10.1
6.7
5.6
2.8

2.9
13.9
11.6
10.4
7
5.8
2.9

3
14.4
12
10.8
7.2
6
3

• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Any unused solution should be discarded according to institutional procedures for antineoplastics.

Admixture Stability

• Bendeka contains no antimicrobial preservative. Prepare the admixture as close as possible to the time of patient administration.
• If diluted with 0.9% Sodium Chloride Injection, USP, or 2.5% Dextrose/0.45% Sodium Chloride Injection, USP, the final admixture is stable for 24 hours when stored refrigerated (2-8°C or 36-46°F) or for 6 hours when stored at room temperature (15-30°C or 59-86°F) and room light. Administration of diluted
  Bendeka (bendamustine hydrochloride) injection must be completed within this period of time.
• In the event that 5% Dextrose Injection, USP is utilized, the final admixture is stable for 24 hours when stored refrigerated (2-8°C or 36-46°F) or for only 3 hours when stored at room temperature (15-30°C or 59-86°F) and room light. Administration of diluted
  Bendeka must be completed within this period of time.
• Retain the partially used vial in original package to protect from light and store refrigerated (2-8°C or 36-46°F) if additional dose withdrawal from the same vial is intended.

Stability Of Partially Used Vials (Needle Punched Vials)

• Bendeka is supplied in a multiple-dose vial. Although it does not contain any antimicrobial preservative,
  Bendeka is bacteriostatic.
• The partially used vials are stable for up to 28 days when stored in its original carton under refrigeration (2-8°C or 36-46°F). Each vial is not recommended for more than a total of six (6) dose withdrawals.
• After first use, store the partially used vial in the refrigerator in the original carton at 2°-8°C or 36-46°F and then discard after 28 days.

What drugs interact with Bendeka?

CYP1A2 Inhibitors

• The coadministration of Bendeka with CYP1A2 inhibitors may increase
  bendamustine plasma concentrations and may result in increased incidence of
  adverse reactions with Bendeka.
• Consider alternative therapies that are not CYP1A2 inhibitors during treatment with
  Bendeka.

CYP1A2 Inducers

• The coadministration of Bendeka with CYP1A2 inducers may decrease
  bendamustine plasma concentrations and may result in decreased efficacy of
  Bendeka.
• Consider alternative therapies that are not CYP1A2 inducers during treatment with
  Bendeka.

Is Bendeka safe to use while pregnant or breastfeeding?

• There are no available data on bendamustine hydrochloride use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.
• There are no data on the presence of bendamustine hydrochloride or its metabolites in either human or animal milk, the effects on the breastfed child, or the effects on milk production.
• Because of the potential for serious adverse reactions in the breastfed child, advise patients that breastfeeding is not recommended during treatment with
  Bendeka, and for at least 1 week after the last dose.