ASH News Daily 2017 - Issue 3 - B-54

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Brief Summary (cont'd)
Table 5: Thrombocytopenia and Neutropenia (pooled adverse event
and laboratory data)
NINLARO +
Lenalidomide and
Dexamethasone
N=360

Placebo +
Lenalidomide and
Dexamethasone
N=360

N (%)

Any Grade

Grade 3-4

Any Grade

Grade 3-4

Thrombocytopenia

281 (78)

93 (26)

196 (54)

39 (11)

Neutropenia

240 (67)

93 (26)

239 (66)

107 (30)

IXAZ17CDNY1359_Brief_Summary_Sept_2017_Update_r3.indd 2

Please see full Prescribing Information for NINLARO at NINLARO-hcp.com.
All trademarks are the property of their respective owners.
©2017 Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of
Takeda Pharmaceutical Company Limited. All rights reserved.
SEPT 2017

USO/IXA/15/0123(4)

9/20/17 4:53 PM

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Herpes Zoster
Herpes zoster was reported in 4% of patients in the NINLARO regimen and 2%
of patients in the placebo regimen. Antiviral prophylaxis was allowed at the
physician's discretion. Patients treated in the NINLARO regimen who received
antiviral prophylaxis had a lower incidence (< 1%) of herpes zoster infection
compared to patients who did not receive prophylaxis (6%).
Eye Disorders
Eye disorders were reported with many different preferred terms but in
aggregate, the frequency was 26% in patients in the NINLARO regimen and
16% of patients in the placebo regimen. The most common adverse reactions
were blurred vision (6% in the NINLARO regimen and 3% in the placebo
regimen), dry eye (5% in the NINLARO regimen and 1% in the placebo regimen),
and conjunctivitis (6% in the NINLARO regimen and 1% in the placebo regimen).
Grade 3 adverse reactions were reported in 2% of patients in the NINLARO
regimen and 1% in the placebo regimen.
The following serious adverse reactions have each been reported at a frequency
of < 1%: acute febrile neutrophilic dermatosis (Sweet's syndrome), StevensJohnson syndrome, transverse myelitis, posterior reversible encephalopathy
syndrome, tumor lysis syndrome, and thrombotic thrombocytopenic purpura.
7 DRUG INTERACTIONS
7.1 Strong CYP3A Inducers: Avoid concomitant administration of NINLARO
with strong CYP3A inducers (such as rifampin, phenytoin, carbamazepine, and
St. John's Wort).
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy:
Risk Summary: Based on its mechanism of action and data from animal
reproduction studies, NINLARO can cause fetal harm when administered to a
pregnant woman. There are no human data available regarding the potential
effect of NINLARO on pregnancy or development of the embryo or fetus.
Ixazomib caused embryo-fetal toxicity in pregnant rats and rabbits at doses
resulting in exposures that were slightly higher then those observed in patients
receiving the recommended dose. Advise women of the potential risk to a fetus
and to avoid becoming pregnant while being treated with NINLARO. In the
U.S. general population, the estimated background risk of major birth defects
and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%,
respectively. Animal Data: In an embryo-fetal development study in pregnant
rabbits there were increases in fetal skeletal variations/abnormalities (caudal
vertebrae, number of lumbar vertebrae, and full supernumerary ribs) at doses
that were also maternally toxic (≥ 0.3 mg/kg). Exposures in the rabbit at 0.3 mg/kg
were 1.9 times the clinical time averaged exposures at the recommended dose
of 4 mg. In a rat dose range-finding embryo-fetal development study, at doses
that were maternally toxic, there were decreases in fetal weights, a trend
towards decreased fetal viability, and increased post-implantation losses
at 0.6 mg/kg. Exposures in rats at the dose of 0.6 mg/kg was 2.5 times the
clinical time averaged exposures at the recommended dose of 4 mg.
8.2 Lactation: No data are available regarding the presence of NINLARO or
its metabolites in human milk, the effects of the drug on the breast fed
infant, or the effects of the drug on milk production. Because the potential
for serious adverse reactions from NINLARO in breastfed infants is unknown,
advise nursing women not to breastfeed during treatment with NINLARO and
for 90 days after the last dose.
8.3 Females and Males of Reproductive Potential: Contraception - Male and
female patients of childbearing potential must use effective contraceptive
measures during and for 90 days following treatment. Dexamethasone is known
to be a weak to moderate inducer of CYP3A4 as well as other enzymes and
transporters. Because NINLARO is administered with dexamethasone, the risk
for reduced efficacy of contraceptives needs to be considered. Advise women
using hormonal contraceptives to also use a barrier method of contraception.
8.4 Pediatric Use: Safety and effectiveness have not been established in
pediatric patients.
8.5 Geriatric Use: Of the total number of subjects in clinical studies of
NINLARO, 55% were 65 and over, while 17% were 75 and over. No overall
differences in safety or effectiveness were observed between these subjects
and younger subjects, and other reported clinical experience has not identified

differences in responses between the elderly and younger patients, but greater
sensitivity of some older individuals cannot be ruled out.
8.6 Hepatic Impairment: In patients with moderate or severe hepatic impairment,
the mean AUC increased by 20% when compared to patients with normal hepatic
function. Reduce the starting dose of NINLARO in patients with moderate or severe
hepatic impairment.
8.7 Renal Impairment: In patients with severe renal impairment or ESRD requiring
dialysis, the mean AUC increased by 39% when compared to patients with normal
renal function. Reduce the starting dose of NINLARO in patients with severe renal
impairment or ESRD requiring dialysis. NINLARO is not dialyzable and therefore
can be administered without regard to the timing of dialysis
10 OVERDOSAGE: There is no known specific antidote for NINLARO overdose.
In the event of an overdose, monitor the patient for adverse reactions and
provide appropriate supportive care.
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Dosing Instructions
* Instruct patients to take NINLARO exactly as prescribed.
* Advise patients to take NINLARO once a week on the same day and at
approximately the same time for the first three weeks of a four week cycle.
* Advise patients to take NINLARO at least one hour before or at least two
hours after food.
* Advise patients that NINLARO and dexamethasone should not be taken at the
same time, because dexamethasone should be taken with food and
NINLARO should not be taken with food.
* Advise patients to swallow the capsule whole with water. The capsule should
not be crushed, chewed or opened.
* Advise patients that direct contact with the capsule contents should be
avoided. In case of capsule breakage, avoid direct contact of capsule
contents with the skin or eyes. If contact occurs with the skin, wash
thoroughly with soap and water. If contact occurs with the eyes, flush
thoroughly with water.
* If a patient misses a dose, advise them to take the missed dose as long as
the next scheduled dose is ≥ 72 hours away. Advise patients not to take a
missed dose if it is within 72 hours of their next scheduled dose.
* If a patient vomits after taking a dose, advise them not to repeat the dose but
resume dosing at the time of the next scheduled dose.
* Advise patients to store capsules in original packaging, and not to remove the
capsule from the packaging until just prior to taking NINLARO.
Thrombocytopenia: Advise patients that they may experience low platelet
counts (thrombocytopenia). Signs of thrombocytopenia may include bleeding
and easy bruising.
Gastrointestinal Toxicities: Advise patients they may experience diarrhea,
constipation, nausea and vomiting and to contact their physician if these
adverse reactions persist.
Peripheral Neuropathy: Advise patients to contact their physicians if they
experience new or worsening symptoms of peripheral neuropathy such as
tingling, numbness, pain, a burning feeling in the feet or hands, or weakness in
the arms or legs.
Peripheral Edema: Advise patients to contact their physicians if they
experience unusual swelling of their extremities or weight gain due to swelling.
Cutaneous Reactions: Advise patients to contact their physicians if they
experience new or worsening rash
Hepatotoxicity: Advise patients to contact their physicians if they experience
jaundice or right upper quadrant abdominal pain
Other Adverse Reactions: Advise patients to contact their physicians if they
experience signs and symptoms of acute febrile neutrophilic dermatosis
(Sweet's syndrome), Stevens-Johnson syndrome, transverse myelitis, posterior
reversible encephalopathy syndrome, tumor lysis syndrome, and thrombotic
thrombocytopenic purpura
Pregnancy: Advise women of the potential risk to a fetus and to avoid becoming
pregnant while being treated with NINLARO and for 90 days following the final
dose. Advise women using hormonal contraceptives to also use a barrier
method of contraception. Advise patients to contact their physicians immediately
if they or their female partner become pregnant during treatment or within 90
days of the final dose.
Concomitant Medications: Advise patients to speak with their physicians
about any other medication they are currently taking and before starting any
new medications.

Table of Contents for the Digital Edition of ASH News Daily 2017 - Issue 3