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Bendeka

Last reviewed on RxList: 8/9/2018
Bendeka Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

Last reviewed on RxList 8/9/2018

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. 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).

The dosing and dosage regimen for Bendeka depends on the condition being treated. Bendeka may interact with fluvoxamine, ciprofloxacin, omeprazole, and smoking. Tell your doctor all medications and supplements you use. Bendeka is not recommended for use during pregnancy; it may harm a fetus. It is unknown if Bendeka passes into breast milk. Consult your doctor before breastfeeding.

Our Bendeka (bendamustine hydrochloride) Injection Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Bendeka Professional Information

SIDE EFFECTS

The following serious adverse reactions have been associated with bendamustine hydrochloride in clinical trials and are discussed in greater detail in other sections of the prescribing information.

Adverse Events In Clinical Trials

The data described below reflect exposure to bendamustine hydrochloride in 329 patients who participated in an actively controlled trial (N=153) for the treatment of CLL and two single arm studies (N=176) for the treatment of indolent B cell NHL. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of BENDEKA (bendamustine hydrochloride) injection administered IV as a 50 mL admixture over a 10-minute infusion is supported by clinical trials using bendamustine hydrochloride administered IV as a 500 mL admixture over 30-60 minutes infusion time, as well as an open-label, crossover study in 81 'end-of-life' cancer patients treated with BENDEKA. In total, safety data from clinical studies are available from over 400 cancer patients exposed to bendamustine hydrochloride at doses in the range used in the treatment of CLL and NHL.

No clinically significant differences in the adverse event profile were noted among bendamustine hydrochloride administered as a 500 mL admixture over standard infusion time (30-60 minutes) and BENDEKA administered as a 50 mL admixture in a 'short-time' infusion over 10 minutes.

The safety and tolerability of BENDEKA was evaluated in an 8-week clinical study of BENDEKA in 81 'end-of-life' cancer patients, diagnosed with solid tumors and hematologic malignancies (excluding CLL). The population was 40-82 years of age, 58% females, 84% white, 12.3% Black, 1.2% Asian and 2.5% were classified as 'other'. BENDEKA was administered IV at a 120 mg/m² dose as a 50 mL admixture over 10 minutes. Patients in the study received BENDEKA (50 mL IV, over 10 minutes) or bendamustine hydrochloride (500 mL IV, over 60 minutes) on Days 1 and 2 every 28 days for two consecutive 2-day cycles.

Adverse reactions (any grade) that occurred with a frequency greater than 5% during BENDEKA infusion and within one hour post-infusion were nausea (8.2%) and fatigue (5.5%).

Adverse reactions (any grade) that occurred with a frequency greater than 5% within 24 hours of BENDEKA were nausea (10.9%) and fatigue (8.2%).

Adverse reactions leading to study withdrawal in 4 patients receiving BENDEKA were pyrexia (1.2%), nausea (1.2%), vomiting (1.2%), pneumonia (1.2%) and fatigue (1.2%).

Clinical Trials Experience In CLL

The data described below reflect exposure to bendamustine hydrochloride in 153 patients. Bendamustine hydrochloride was studied in an active-controlled randomized trial. The population was 45-77 years of age, 63% male, 100% white, and had treatment naive CLL. All patients started the study at a dose of 100 mg/m² intravenously over 30 minutes on Days 1 and 2 every 28 days.

Adverse reactions were reported according to NCI CTC v.2.0. In the randomized CLL clinical study, non-hematologic adverse reactions (any grade) in the bendamustine hydrochloride group that occurred with a frequency greater than 15% were pyrexia (24%), nausea (20%), and vomiting (16%).

Other adverse reactions seen frequently in one or more studies included asthenia, fatigue, malaise, and weakness; dry mouth; somnolence; cough; constipation; headache; mucosal inflammation and stomatitis.

Worsening hypertension was reported in 4 patients treated with bendamustine hydrochloride in the randomized CLL clinical study and in none treated with chlorambucil. Three of these 4 adverse reactions were described as a hypertensive crisis and were managed with oral medications and resolved.

The most frequent adverse reactions leading to study withdrawal for patients receiving bendamustine hydrochloride were hypersensitivity (2%) and pyrexia (1%).

Table 1 contains the treatment emergent adverse reactions, regardless of attribution, that were reported in ≥ 5% of patients in either treatment group in the randomized CLL clinical study.

Table 1: Non-Hematologic Adverse Reactions Occurring in Randomized CLL Clinical Study in at Least 5% of Patients

System organ class Preferred term Number (%) of patients
Bendamustine Hydrochloride
(N=153)
Chlorambucil
(N=143)
All Grades Grade 3/4 All Grades Grade 3/4
Total number of patients with at least 1 adverse reaction 121 (79) 52 (34) 96 (67) 25 (17)
Gastrointestinal disorders
Nausea 31 (20) 1 (<1) 21 (15) 1 (<1)
Vomiting 24 (16) 1 (<1) 9 (6) 0
Diarrhea 14 (9) 2 (1) 5 (3) 0
General disorders and administration site conditions
Pyrexia 36 (24) 6 (4) 8 (6) 2 (1)
Fatigue 14 (9) 2 (1) 8 (6) 0
Asthenia 13 (8) 0 6 (4) 0
Chills 9 (6) 0 1 (<1) 0
Immune system disorders
Hypersensitivity 7 (5) 2 (1) 3 (2) 0
Infections and infestations
Nasopharyngitis 10 (7) 0 12 (8) 0
Infection 9 (6) 3 (2) 1 (<1) 1 (<1)
Herpes simplex 5 (3) 0 7 (5) 0
Investigations
Weight decreased 11 (7) 0 5 (3) 0
Metabolism and nutrition disorders
Hyperuricemia 11 (7) 3 (2) 2 (1) 0
Respiratory, thoracic and mediastinal disorders
Cough 6 (4) 1 (<1) 7 (5) 1 (<1)
Skin and subcutaneous tissue disorders
Rash 12 (8) 4 (3) 7 (5) 3 (2)
Pruritus 8 (5) 0 2 (1) 0

The Grade 3 and 4 hematology laboratory test values by treatment group in the randomized CLL clinical study are described in Table 2. These findings confirm the myelosuppressive effects seen in patients treated with bendamustine hydrochloride. Red blood cell transfusions were administered to 20% of patients receiving bendamustine hydrochloride compared with 6% of patients receiving chlorambucil.

Table 2: Incidence of Hematology Laboratory Abnormalities in Patients Who Received bendamustine hydrochloride or Chlorambucil in the Randomized CLL Clinical Study

Laboratory Abnormality Bendamustine Hydrochloride
N=150
Chlorambucil
N=141
All Grades
n (%)
Grade 3/4
n (%)
All Grades
n (%)
Grade 3/4
n (%)
Hemoglobin Decreased 134 (89) 20 (13) 115 (82) 12 (9)
Platelets Decreased 116 (77) 16 (11) 110 (78) 14 (10)
Leukocytes Decreased 92 (61) 42 (28) 26 (18) 4 (3)
Lymphocytes Decreased 102 (68) 70 (47) 27 (19) 6 (4)
Neutrophils Decreased 113 (75) 65 (43) 86 (61) 30 (21)

In the randomized CLL trial, 34% of patients had bilirubin elevations, some without associated significant elevations in AST and ALT. Grade 3 or 4 increased bilirubin occurred in 3% of patients. Increases in AST and ALT of Grade 3 or 4 were limited to 1% and 3% of patients, respectively. Patients treated with bendamustine hydrochloride may also have changes in their creatinine levels. If abnormalities are detected, monitoring of these parameters should be continued to ensure that significant deterioration does not occur.

Clinical Trials Experience In NHL

The data described below reflect exposure to bendamustine hydrochloride in 176 patients with indolent B-cell NHL treated in two single-arm studies. The population was 31-84 years of age, 60% male, and 40% female. The race distribution was 89% White, 7% Black, 3% Hispanic, 1% other, and <1% Asian. These patients received bendamustine hydrochloride at a dose of 120 mg/m² intravenously on Days 1 and 2 for up to eight 21-day cycles.

The adverse reactions occurring in at least 5% of the NHL patients, regardless of severity, are shown in Table 3. The most common non-hematologic adverse reactions (≥30%) were nausea (75%), fatigue (57%), vomiting (40%), diarrhea (37%) and pyrexia (34%). The most common non-hematologic Grade 3 or 4 adverse reactions (≥5%) were fatigue (11%), febrile neutropenia (6%), and pneumonia, hypokalemia and dehydration, each reported in 5% of patients.

Table 3: Non-Hematologic Adverse Reactions Occurring in at Least 5% of NHL Patients Treated with bendamustine hydrochloride by System Organ Class and Preferred Term (N=176)

System organ class
Preferred Term
Number (%) of patients*
All Grades Grade 3/4
Total number of patients with at least 1 adverse reaction 176 (100) 94 (53)
Cardiac Disorders
Tachycardia 13 (7) 0
Gastrointestinal disorders
Nausea 132 (75) 7 (4)
Vomiting 71 (40) 5 (3)
Diarrhea 65 (37) 6 (3)
Constipation 51 (29) 1 (<1)
Stomatitis 27 (15) 1 (<1)
Abdominal pain 22 (13) 2 (1)
Dyspepsia 20 (11) 0
Gastroesophageal reflux disease 18 (10) 0
Dry mouth 15 (9) 1 (<1)
Abdominal pain upper 8 (5) 0
Abdominal distension 8 (5) 0
General disorders and administration site conditions
Fatigue 101 (57) 19 (11)
Pyrexia 59 (34) 3 (2)
Chills 24 (14) 0
Edema peripheral 23(13) 1 (<1)
Asthenia 19 (11) 4 (2)
Chest pain 11 (6) 1 (<1)
Infusion site pain 11 (6) 0
Pain 10 (6) 0
Catheter site pain 8 (5) 0
Infections and infestations
Herpes zoster 18 (10) 5 (3)
Upper respiratory tract infection 18 (10) 0
Urinary tract infection 17 (10) 4 (2)
Sinusitis 15 (9) 0
Pneumonia 14 (8) 9 (5)
Febrile neutropenia 11 (6) 11 (6)
Oral candidiasis 11 (6) 2 (1)
Nasopharyngitis 11 (6) 0
Investigations
Weight decreased 31 (18) 3 (2)
Metabolism and nutrition disorders
Anorexia 40 (23) 3 (2)
Dehydration 24 (14) 8 (5)
Decreased appetite 22 (13) 1 (<1)
Hypokalemia 15 (9) 9 (5)
Musculoskeletal and connective tissue disorders
Preferred Term All Grades Grade 3/4
Back pain 25 (14) 5 (3)
Arthralgia 11 (6) 0
Pain in extremity 8 (5) 2 (1)
Bone pain 8 (5) 0
Nervous system disorders
Headache 36 (21) 0
Dizziness 25 (14) 0
Dysgeusia 13 (7) 0
Psychiatric disorder
Insomnia 23(13) 0
Anxiety 14 (8) 1 (<1)
Depression 10 (6) 0
Respiratory, thoracic and mediastinal disorders
Cough 38 (22) 1 (<1)
Dyspnea 28 (16) 3 (2)
Pharyngolaryngeal pain 14 (8) 1 (<1)
Wheezing 8 (5) 0
Nasal congestion 8 (5) 0
Skin and subcutaneous tissue disorders
Rash 28 (16) 1 (<1)
Pruritus 11 (6) 0
Dry skin 9 (5) 0
Night sweats 9 (5) 0
Hyperhidrosis 8 (5) 0
Vascular disorders
Hypotension 10 (6) 2 (1)
*Patients may have reported more than 1 adverse reaction.

NOTE: Patients counted only once in each preferred term category and once in each system organ class category.

Hematologic toxicities, based on laboratory values and CTC grade, in NHL patients treated in both single arm studies combined are described in Table 4. Clinically important chemistry laboratory values that were new or worsened from baseline and occurred in >1% of patients at grade 3 or 4, in NHL patients treated in both single arm studies combined were hyperglycemia (3%), elevated creatinine (2%), hyponatremia (2%), and hypocalcemia (2%).

Table 4: Incidence of Hematology Laboratory Abnormalities in Patients Who Received bendamustine hydrochloride in the NHL Studies

Hematology Variable Percent of Patients
All Grades Grade 3/4
Lymphocytes Decreased 99 94
Leukocytes Decreased 94 56
Hemoglobin Decreased 88 11
Neutrophils Decreased 86 60
Platelets Decreased 86 25

In both studies, serious adverse reactions, regardless of causality, were reported in 37% of patients receiving bendamustine hydrochloride. The most common serious adverse reactions occurring in ≥5% of patients were febrile neutropenia and pneumonia. Other important serious adverse reactions reported in clinical trials and/or postmarketing experience were acute renal failure, cardiac failure, hypersensitivity, skin reactions, pulmonary fibrosis, and myelodysplastic syndrome.

Serious drug-related adverse reactions reported in clinical trials included myelosuppression, infection, pneumonia, tumor lysis syndrome and infusion reactions. [see WARNINGS AND PRECAUTIONS] Adverse reactions occurring less frequently but possibly related to bendamustine hydrochloride treatment were hemolysis, dysgeusia/taste disorder, atypical pneumonia, sepsis, herpes zoster, erythema, dermatitis, and skin necrosis.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of bendamustine hydrochloride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and lymphatic systems disorders: Pancytopenia.

Cardiovascular disorders: Atrial fibrillation, congestive heart failure (some fatal), myocardial infarction (some fatal), palpitation.

General disorders and administration site conditions: Injection site reactions (including phlebitis, pruritus, irritation, pain, swelling), infusion site reactions (including phlebitis, pruritus, irritation, pain, swelling).

Immune system disorders: Anaphylaxis.

Infections and infestations: Pneumocystis jiroveci pneumonia.

Respiratory, thoracic and mediastinal disorders: Pneumonitis.

Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome, Toxic epidermal necrolysis, DRESS (Drug reaction with eosinophilia and systemic symptoms). [see WARNINGS AND PRECAUTIONS]

Read the entire FDA prescribing information for Bendeka (Bendamustine Hydrochloride Injection)

Related Resources for Bendeka

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© Bendeka Patient Information is supplied by Cerner Multum, Inc. and Bendeka Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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