ASH Clinical News Focus on Myeloid Malignancies | Page 9

BENDEKA ® (bendamustine hydrochloride) injection BENDEKA ® (bendamustine hydrochloride) injection
System organ class
Number (%) of patients*
Preferred Term
All Grades
Grade 3/4
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
Percent of Patients
Hematology Variable
All Grades
Grade 3/4
Lymphocytes De creased
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. 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.
6.4
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).
7
DRUG INTERACTIONS
No formal clinical assessments of pharmacokinetic drug-drug interactions
between bendamustine hydrochloride and other drugs have been conducted.
Bendamustine’s active metabolites, gamma-hydroxy bendamustine (M3)
and N-desmethyl-bendamustine (M4), are formed via cytochrome P450
CYP1A2. Inhibitors of CYP1A2 (e.g., fluvoxamine, ciprofloxacin) have
potential to increase plasma concentrations of bendamustine and decrease
plasma concentrations of active metabolites. Inducers of CYP1A2 (e.g.,
omeprazole, smoking) have potential to decrease plasma concentrations of
bendamustine and increase plasma concentrations of its active metabolites.
Caution should be used, or alternative treatments considered if concomitant
treatment with CYP1A2 inhibitors or inducers is needed. The role of active transport systems in bendamustine distribution has not
been fully evaluated. In vitro data suggest that P-glycoprotein, breast cancer
resistance protein (BCRP), and/or other efflux transporters may have a role in
bendamustine transport.
Based on in vitro data, bendamustine is not likely to inhibit metabolism via
human CYP isoenzymes CYP1A2, 2C9/10, 2D6, 2E1, or 3A4/5, or to induce
metabolism of substrates of cytochrome P450 enzymes.
8.6
Renal Impairment
No formal studies assessing the impact of renal impairment on the pharma-
cokinetics of bendamustine have been conducted. BENDEKA (bendamustine
hydrochloride) injection should be used with caution in patients with mild or
moderate renal impairment. BENDEKA (bendamustine hydrochloride) injec-
tion should not be used in patients with CrCL < 40 mL/min.
8.7
Hepatic Impairment
No formal studies assessing the impact of hepatic impairment on the pharma-
cokinetics of bendamustine have been conducted. BENDEKA (bendamustine
hydrochloride) injection should be used with caution in patients with mild
hepatic impairment. BENDEKA (bendamustine hydrochloride) injection should
not be used in patients with moderate (AST or ALT 2.5-10 X ULN and total
bilirubin 1.5-3 X ULN) or severe (total bilirubin > 3 X ULN) hepatic impairment.
16.1 Safe Handling and Disposal
BENDEKA (bendamustine hydrochloride) injection is a cytotoxic drug.
Follow applicable special handling and disposal procedures. 1 Care should
be exercised in the handling and preparation of solutions prepared from
BENDEKA (bendamustine hydrochloride) injection. The use of gloves and
safety glasses is recommended to avoid exposure in case of breakage of the
vial or other accidental spillage. If a solution of BENDEKA (bendamustine
hydrochloride) injection contacts the skin, wash the skin immediately and
thoroughly with soap and water. If BENDEKA (bendamustine hydrochloride)
injection contacts the mucous membranes, flush thoroughly with water.
16.3 Storage
Store BENDEKA (bendamustine hydrochloride) injection in refrigerator,
2°-8°C (36°-46°F). Retain in original carton until time of use to protect from
light.
Distributed By:
Teva Pharmaceuticals USA, Inc.
North Wales, PA 19454
Rev. 02/2017
All rights reserved.
This Brief Summary is based on the Full Prescribing Information for BENDEKA
BEN-004.
BEN-40461 April 2017