ASH News Daily 2017 - Issue 3 - B-53
T:7"
BRIEF SUMMARY OF PRESCRIBING INFORMATION
NINLARO (ixazomib) capsules, for oral use
1 INDICATION
NINLARO (ixazomib) is indicated in combination with lenalidomide and
dexamethasone for the treatment of patients with multiple myeloma who have
received at least one prior therapy.
IXAZ17CDNY1359_Brief_Summary_Sept_2017_Update_r3.indd 1
6 ADVERSE REACTIONS
The following adverse reactions are described in detail in other sections of the
prescribing information:
* Thrombocytopenia [see Warnings and Precautions (5.1)]
* Gastrointestinal Toxicities [see Warnings and Precautions (5.2)]
* Peripheral Neuropathy [see Warnings and Precautions (5.3)]
* Peripheral Edema [see Warnings and Precautions (5.4)]
* Cutaneous Reactions [see Warnings and Precautions (5.5)]
* Hepatotoxicity [see Warnings and Precautions (5.6)]
6.1 CLINICAL TRIALS EXPERIENCE
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 population from the randomized, double-blind, placebo-controlled
clinical study included 720 patients with relapsed and/or refractory multiple
myeloma, who received NINLARO in combination with lenalidomide and
dexamethasone (NINLARO regimen; N=360) or placebo in combination with
lenalidomide and dexamethasone (placebo regimen; N=360).
The most frequently reported adverse reactions (≥ 20%) in the NINLARO
regimen and greater than the placebo regimen were diarrhea, constipation,
thrombocytopenia, peripheral neuropathy, nausea, peripheral edema,
vomiting, and back pain. Serious adverse reactions reported in ≥ 2% of
patients included thrombocytopenia (2%) and diarrhea (2%). For each
adverse reaction, one or more of the three drugs was discontinued in ≤ 1%
of patients in the NINLARO regimen.
Table 4: Non-Hematologic Adverse Reactions Occurring in ≥ 5% of
Patients with a ≥ 5% Difference Between the NINLARO Regimen and the
Placebo Regimen (All Grades, Grade 3 and Grade 4)
NINLARO +
Lenalidomide and
Dexamethasone
N=360
Placebo +
Lenalidomide and
Dexamethasone
N=360
N (%)
N (%)
System Organ Class /
Preferred Term
All
Grade
3
Grade
4
All
Grade
3
Grade
4
Infections and infestations
Upper respiratory tract
infection
69 (19)
1 (< 1)
0
52 (14)
2 (< 1)
0
Nervous system disorders
Peripheral neuropathies*
100 (28)
7 (2)
0
77 (21)
7 (2)
0
Gastrointestinal disorders
Diarrhea
Constipation
Nausea
Vomiting
151 (42)
122 (34)
92 (26)
79 (22)
22 (6)
1 (< 1)
6 (2)
4 (1)
0
0
0
0
130 (36)
90 (25)
74 (21)
38 (11)
8 (2)
1 (< 1)
0
2 (< 1)
0
0
0
0
Skin and subcutaneous
tissue disorders
Rash*
68 (19)
9 (3)
0
38 (11)
5 (1)
0
Musculoskeletal and
connective tissue disorders
Back pain
74 (21)
2 (< 1)
0
57 (16)
9 (3)
0
General disorders and
administration site
conditions
Edema peripheral
91 (25)
8 (2)
0
66 (18)
4 (1)
0
Note: Adverse reactions included as preferred terms are based on MedDRA
version 16.0.
*Represents a pooling of preferred terms
(Continued on next page)
9/20/17 4:53 PM
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5 WARNINGS AND PRECAUTIONS
5.1 Thrombocytopenia: Thrombocytopenia has been reported with NINLARO
with platelet nadirs typically occurring between Days 14-21 of each 28-day
cycle and recovery to baseline by the start of the next cycle. Three percent
of patients in the NINLARO regimen and 1% of patients in the placebo
regimen had a platelet count ≤ 10,000/mm3 during treatment. Less than 1% of
patients in both regimens had a platelet count ≤ 5000/mm3 during treatment.
Discontinuations due to thrombocytopenia were similar in both regimens (< 1%
of patients in the NINLARO regimen and 2% of patients in the placebo regimen
discontinued one or more of the three drugs).The rate of platelet transfusions
was 6% in the NINLARO regimen and 5% in the placebo regimen.
Monitor platelet counts at least monthly during treatment with NINLARO.
Consider more frequent monitoring during the first three cycles. Manage
thrombocytopenia with dose modifications and platelet transfusions as per
standard medical guidelines.
5.2 Gastrointestinal Toxicities: Diarrhea, constipation, nausea, and vomiting,
have been reported with NINLARO, occasionally requiring use of antidiarrheal
and antiemetic medications, and supportive care. Diarrhea was reported in 42%
of patients in the NINLARO regimen and 36% in the placebo regimen,
constipation in 34% and 25%, respectively, nausea in 26% and 21%,
respectively, and vomiting in 22% and 11%, respectively. Diarrhea resulted in
discontinuation of one or more of the three drugs in 1% of patients in the
NINLARO regimen and < 1% of patients in the placebo regimen. Adjust dosing
for Grade 3 or 4 symptoms.
5.3 Peripheral Neuropathy: The majority of peripheral neuropathy adverse
reactions were Grade 1 (18% in the NINLARO regimen and 14% in the placebo
regimen) and Grade 2 (8% in the NINLARO regimen and 5% in the placebo
regimen). Grade 3 adverse reactions of peripheral neuropathy were reported at
2% in both regimens; there were no Grade 4 or serious adverse reactions.
The most commonly reported reaction was peripheral sensory neuropathy (19%
and 14% in the NINLARO and placebo regimen, respectively). Peripheral motor
neuropathy was not commonly reported in either regimen (< 1%). Peripheral
neuropathy resulted in discontinuation of one or more of the three drugs in 1%
of patients in both regimens. Patients should be monitored for symptoms of
neuropathy. Patients experiencing new or worsening peripheral neuropathy may
require dose modification.
5.4 Peripheral Edema: Peripheral edema was reported in 25% and 18% of
patients in the NINLARO and placebo regimens, respectively. The majority
of peripheral edema adverse reactions were Grade 1 (16% in the NINLARO
regimen and 13% in the placebo regimen) and Grade 2 (7% in the NINLARO
regimen and 4% in the placebo regimen).
Grade 3 peripheral edema was reported in 2% and 1% of patients in the
NINLARO and placebo regimens, respectively. There was no Grade 4 peripheral
edema reported. There were no discontinuations reported due to peripheral
edema. Evaluate for underlying causes and provide supportive care, as
necessary. Adjust dosing of dexamethasone per its prescribing information or
NINLARO for Grade 3 or 4 symptoms.
5.5 Cutaneous Reactions: Rash was reported in 19% of patients in the
NINLARO regimen and 11% of patients in the placebo regimen. The majority of
the rash adverse reactions were Grade 1 (10% in the NINLARO regimen and 7%
in the placebo regimen) or Grade 2 (6% in the NINLARO regimen and 3% in the
placebo regimen). Grade 3 rash was reported in 3% of patients in the NINLARO
regimen and 1% of patients in the placebo regimen. There were no Grade 4 or
serious adverse reactions of rash reported. The most common type of rash
reported in both regimens included maculo-papular and macular rash. Rash
resulted in discontinuation of one or more of the three drugs in < 1% of patients
in both regimens. Manage rash with supportive care or with dose modification
if Grade 2 or higher.
5.6 Hepatotoxicity: Drug-induced liver injury, hepatocellular injury, hepatic
steatosis, hepatitis cholestatic and hepatotoxicity have each been reported in
< 1% of patients treated with NINLARO. Events of liver impairment have been
reported (6% in the NINLARO regimen and 5% in the placebo regimen). Monitor
hepatic enzymes regularly and adjust dosing for Grade 3 or 4 symptoms.
5.7 Embryo-Fetal Toxicity: NINLARO can cause fetal harm when administered
to a pregnant woman based on the mechanism of action and findings in
animals. There are no adequate and well-controlled studies in pregnant women
using NINLARO. Ixazomib caused embryo-fetal toxicity in pregnant rats and
rabbits at doses resulting in exposures that were slightly higher than those
observed in patients receiving the recommended dose.
Females of reproductive potential should be advised to avoid becoming pregnant
while being treated with NINLARO. If NINLARO is used during pregnancy or if the
patient becomes pregnant while taking NINLARO, the patient should be apprised
of the potential hazard to the fetus. Advise females of reproductive potential that
they must use effective contraception during treatment with NINLARO and for 90
days following the final dose. Women using hormonal contraceptives should also
use a barrier method of contraception.
Table of Contents for the Digital Edition of ASH News Daily 2017 - Issue 3
ASH News Daily 2017 - Issue 3 - A-1
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ASH News Daily 2017 - Issue 3 - A-24
ASH News Daily 2017 - Issue 3 - A-25
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ASH News Daily 2017 - Issue 3 - A-28
ASH News Daily 2017 - Issue 3 - B-1
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ASH News Daily 2017 - Issue 3 - B-53
ASH News Daily 2017 - Issue 3 - B-54
ASH News Daily 2017 - Issue 3 - B-55
ASH News Daily 2017 - Issue 3 - B-56
ASH News Daily 2017 - Issue 3 - C-1
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ASH News Daily 2017 - Issue 3 - C-15
ASH News Daily 2017 - Issue 3 - C-16
ASH News Daily 2017 - Issue 3 - C-17
ASH News Daily 2017 - Issue 3 - C-18
ASH News Daily 2017 - Issue 3 - C-19
ASH News Daily 2017 - Issue 3 - C-20
ASH News Daily 2017 - Issue 3 - C-21
ASH News Daily 2017 - Issue 3 - C-22
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ASH News Daily 2017 - Issue 3 - C-24
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ASH News Daily 2017 - Issue 3 - C-28
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ASH News Daily 2017 - Issue 3 - C-30
ASH News Daily 2017 - Issue 3 - C-31
ASH News Daily 2017 - Issue 3 - C-32
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