Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Myelodysplastic Syndrome/Acute Myeloid Leukemia
Additions and/or
revisions underlined:
Myelodysplastic syndrome/acute myeloid leukemia
(MDS/AML), including cases with a fatal outcome, have been reported in patients
who received ZEJULA.
In PRIMA, MDS/AML occurred in 6 out of 484 (1.2%)
patients treated with ZEJULA and in 3 out of 244 (1.2%) patients treated with
placebo [see Adverse Reactions (6.1)]. The
duration of therapy with ZEJULA in patients who developed secondary MDS/cancer
therapy-related AML varied from 3.7 months to 2.5 years.
In NOVA, of patients within the gBRCAmut
cohort, MDS/AML occurred in 10 out of 136 (7%) patients treated with ZEJULA and
in 2 out of 65 (3%) patients treated with placebo [see Adverse Reactions
(6.1)]. The duration of therapy with ZEJULA in patients who developed
secondary MDS/cancer-therapy related AML varied from 3.6 months to 5.9 years.
All patients who developed secondary MDS/cancer
therapy-related AML had received previous chemotherapy with platinum agents
and/or other DNA-damaging agents, including radiotherapy.
For suspected MDS/AML or prolonged hematological
toxicities, refer the patient to a hematologist for further evaluation. Discontinue ZEJULA if MDS/AML is confirmed.
6
Adverse Reactions
6.1 Clinical Trials Experience
Additions and/or revisions; please refer to label
for complete information.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATION
Additions and/or revisions underlined:
…
What
is ZEJULA?
ZEJULA is a prescription medicine used for the:
…
maintenance treatment of adults with ovarian cancer,
fallopian tube cancer, or primary peritoneal
cancer with a certain type of inherited (germline)
abnormal BRCA gene that comes back. ZEJULA is used after the cancer has responded (complete
or partial response) to treatment with platinum- based chemotherapy. Your
healthcare provider will perform a test to make sure that ZEJULA is
right for you.
…
Approved Drug Label (PDF)
6
Adverse Reactions
6.1 Clinical Trials Experience
Additions and/or
revisions underlined:
Because clinical trials are conducted under widely
varying conditions, adverse reaction rates observed in the clinical trials of a
drug cannot be directly compared with rates in the clinical trials of another
drug and may not reflect the rates observed in practice.
In a pooled safety population of patients (n = 1,314) with advanced ovarian, fallopian tube, or primary
peritoneal cancer treated with ZEJULA monotherapy including PRIMA
(n = 484), NOVA (n = 367), and another clinical trial (n = 463),
the most common adverse reactions >10% were nausea (65%),
thrombocytopenia (60%), anemia (56%), fatigue (55%), constipation (39%),musculoskeletal pain (36%), abdominal pain (35%),
vomiting (33%), neutropenia (31%), decreased appetite (24%), leukopenia (24%), insomnia
(23%), headache (23%), dyspnea (22%), rash (21%), diarrhea (18%), hypertension (17%),
cough (16%), dizziness (14%), acute kidney injury (13%), urinary tract infection (12%), and
hypomagnesemia (11%).
…
Approved Drug Label (PDF)
5
Warnings and Precautions
Additions
and/or revisions underlined:
5.2
Bone Marrow Suppression
Hematologic adverse reactions,
including thrombocytopenia, anemia, neutropenia, and/or pancytopenia
have been reported in patients treated with ZEJULA [see Adverse Reactions (6)].
5.3 Hypertension
and Cardiovascular Effects
Newly
added subsections:
5.4
Posterior Reversible Encephalopathy Syndrome
Posterior reversible encephalopathy
syndrome (PRES) occurred in 0.1% of 2,165 patients treated with ZEJULA in
clinical trials and has also been described in postmarketing reports [see Adverse Reactions (6.2)]. Signs and
symptoms of PRES include seizure, headache, altered mental status, visual
disturbance, or cortical blindness, with or without associated hypertension. A
diagnosis of PRES requires confirmation by brain imaging, preferably magnetic
resonance imaging.
Monitor all patients treated with ZEJULA
for signs and symptoms of PRES. If PRES is suspected, promptly discontinue
ZEJULA and administer appropriate treatment. The safety of reinitiating ZEJULA
in patients previously experiencing PRES is not known.
5.6
Allergic Reactions to FD&C Yellow No. 5 (Tartrazine)
ZEJULA capsules contain FD&C Yellow
No. 5 (tartrazine), which may cause allergic-type reactions (including
bronchial asthma) in certain susceptible persons. Although the overall
incidence of FD&C Yellow No. 5 (tartrazine) sensitivity in the general
population is low, it is frequently seen in patients who also have aspirin
hypersensitivity.
6
Adverse Reactions
Additions
and/or revisions underlined to the bulleted line listing:
MDS/AML [see Warnings and Precautions (5.1)]
Bone
marrow suppression [see Warnings and
Precautions (5.2)]
Hypertension and cardiovascular effects [see Warnings and Precautions (5.3)]
Posterior reversible encephalopathy syndrome [see Warnings and Precautions (5.4)]
6.2
Postmarketing Experience
Additions
and/or revisions underlined:
Blood and Lymphatic System Disorders
Pancytopenia
Psychiatric Disorders
Confusional state/disorientation,
hallucination, cognitive impairment (e.g., memory impairment, concentration
impairment).
Vascular Disorders
Hypertensive crisis
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Hypertension and Cardiovascular
Effects
Posterior Reversible Encephalopathy
Syndrome
Inform patients that they are at risk of
developing posterior reversible encephalopathy syndrome (PRES) that can present
with signs and symptoms including seizure, headaches, altered mental status, or
vision changes. Advise patients to contact their healthcare provider if they
develop any of these signs or symptoms [see
Warnings and
Precautions (5.4)].
Allergic Reactions to FD&C Yellow No.
5 (Tartrazine)
Advise patients that ZEJULA capsules
contain FD&C Yellow No. 5 (tartrazine), which may cause allergic-type
reactions (including bronchial asthma) in certain susceptible persons or in
patients who also have aspirin hypersensitivity [see Warnings and Precautions (5.6)].
PATIENT INFORMATION
What
is the most important information I should know about ZEJULA?
ZEJULA
may cause serious side effects including:
Newly
added information:
Posterior
reversible encephalopathy syndrome (PRES). PRES is a condition that affects
the brain and may happen during treatment with ZEJULA. If you have headache,
vision changes, confusion, or seizure with or without high blood pressure,
please contact your healthcare provider.
Before
taking ZEJULA, tell your healthcare provider about all of your medical
conditions, including if you:
Newly
added information:
are
allergic to FD&C Yellow No. 5 (tartrazine) or aspirin. ZEJULA capsules
contain FD&C Yellow No. 5 (tartrazine), which may cause allergic-type
reactions (including bronchial asthma) in certain people, especially people who
also have an allergy to aspirin.
Approved Drug Label (PDF)
8
Use in Specific Populations
8.7 Hepatic Impairment
Additions
and/or revisions underlined:
For patients with moderate hepatic
impairment, reduce the starting dosage of niraparib to 200 mg once daily [see Dosage and Administration (2.4)]. Niraparib
exposure increased in patients with moderate hepatic impairment [total
bilirubin greater than or equal to1.5 x upper level of normal (ULN) to 3.0 x
ULN and any aspartate transaminase (AST) level]. Monitor patients for
hematologic toxicity and reduce the dose further, if needed [see Dosage and Administration (2.3)].
For patients with mild hepatic
impairment (total bilirubin <1.5 x ULN and any AST level or bilirubin less
than or equal to ULN and AST > ULN), no dose adjustment is needed.
The recommended dose of ZEJULA has
not been established for patients with severe hepatic impairment (total
bilirubin >3.0 x ULN and any AST level) [see
Clinical Pharmacology (12.3)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATION
PATIENT
INFORMATION
Before
taking ZEJULA, tell your healthcare provider about all of your medical
conditions, including if you:
Newly
added information:
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Myelodysplastic Syndrome/Acute Myeloid Leukemia
(additions and
revisions underlined)
Myelodysplastic
Syndrome/Acute Myeloid Leukemia (MDS/AML), including cases with fatal outcome,
have been reported in patients who received ZEJULA monotherapy in clinical trials.
In 1785 patients treated with ZEJULA in clinical trials, MDS/AML
occurred in 15 patients (0.8%).
The
duration of therapy with ZEJULA in patients who developed secondary MDS/cancer
therapy- related AML varied from 0.5 months to 4.9 years. All
of these patients had received previous chemotherapy with platinum agents
and/or other DNA-damaging agents including radiotherapy. Discontinue ZEJULA if
MDS/AML is confirmed.
5.2 Bone Marrow Suppression
(additions
underlined)
![]()
Hematologic
adverse reactions (thrombocytopenia, anemia and neutropenia) have been reported
in patients treated with ZEJULA.
In
PRIMA, the overall incidence of Grade greater than or equal to3
thrombocytopenia, anemia and neutropenia were reported, respectively, in 39%,
31%, and 21% of patients receiving ZEJULA. Discontinuation due to
thrombocytopenia, anemia, and neutropenia occurred, respectively, in 4%, 2%,
and 2% of patients. In patients who were administered a starting dose of ZEJULA
based on baseline weight or platelet count, Grade greater than or equal to 3 thrombocytopenia,
anemia and neutropenia were reported, respectively, in 22%, 23%, and 15% of
patients receiving ZEJULA. Discontinuation due to thrombocytopenia, anemia, and
neutropenia occurred, respectively, in 3%, 3%, and 2% of patients.
In
NOVA,
Grade greater than or equal to 3 thrombocytopenia, anemia and neutropenia were
reported, respectively, in 29%, 25%, and 20% of patients receiving ZEJULA.
Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred,
respectively, in 3%, 1%, and 2% of patients.
In
QUADRA, Grade
greater than or equal to 3 thrombocytopenia, anemia and neutropenia were
reported, respectively, in 28%, 27%, and 13% of patients receiving ZEJULA.
Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred,
respectively, in 4%, 2%, and 1% of patients.
…
5.3 Cardiovascular Effects
(additions
underlined)
Hypertension
and hypertensive crisis have been reported in patients treated with ZEJULA.
![]()
In PRIMA, Grade
3-4 hypertension occurred in 6% of ZEJULA-treated patients compared to 1% of
placebo-treated patients with a median time from first dose to first onset of
43 days (range: 1 to 531 days) and with a median duration of 12 days (range: 1
to 61 days). There were no discontinuations due to hypertension.
![]()
In NOVA, Grade 3-4
hypertension occurred in 9% of ZEJULA-treated patients compared to 2% of
placebo-treated patients with a median time from first dose to first onset of
77 days (range: 4 to 504 days) and with a median duration of 15 days (range: 1
to 86 days). Discontinuation due to hypertension occurred in <1% of
patients.
In
QUADRA, Grade 3-4 hypertension occurred in 5% of ZEJULA-treated patients with a
median time from first dose to first onset of 15 days (range: 1 to 316 days)
and with a median duration of 7 days (range: 1 to 118 days). Discontinuation
due to hypertension occurred in <0.2% of patients.
Monitor
blood pressure and heart rate at least weekly for the first two months, then
monthly for the first year and periodically thereafter during treatment with
ZEJULA. Closely monitor patients with cardiovascular disorders, especially coronary
insufficiency, cardiac arrhythmias, and hypertension. Medically manage hypertension
with antihypertensive medications and adjustment of the ZEJULA dose, if necessary.
6
Adverse Reactions
6.1 Clinical Trials Experience
(extensive
additions and revisions, please refer to label for complete information)
6.2 Postmarketing Experience
(new subsection
added)
The
following adverse reactions have been identified during post-approval use of
ZEJULA. 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.
Immune System
Disorders: hypersensitivity
(including anaphylaxis)
Nervous System Disorders: posterior
reversible encephalopathy syndrome (PRES) Psychiatric Disorders: confusional state/disorientation, hallucination,
cognitive impairment Respiratory,
Thoracic, and Mediastinal Disorders: non-infectious pneumonitis
Skin and Subcutaneous Tissue Disorders: photosensitivity
8
Use in Specific Populations
8.5 Geriatric Use
(additions
underlined)
In
PRIMA, 39% of patients were aged greater than or equal to 65 years and 10%
were aged greater than or equal to 75 years. In NOVA, 35% of
patients were aged greater than or
equal to 65 years and 8% were aged greater than or equal to75 years. No overall
differences in safety and effectiveness of ZEJULA were observed between these
patients and younger patients but greater sensitivity of some older individuals
cannot be ruled out.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
(additions
underlined)
…
Cardiovascular
Effects
Advise
patients to undergo blood pressure and heart rate monitoring at least weekly
for the first two months, then monthly for the first year of treatment, and
then periodically thereafter. Advise patients to contact their healthcare provider
if blood pressure is elevated.
…
PATIENT INFORMATION
(additions and
revisions, please refer to label for complete information)
Approved Drug Label (PDF)
5
Warnings and Precautions
5.1 Myelodysplastic Syndrome/Acute Myeloid Leukemia
(additions and/or
revisions are underlined)
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML),
including cases with fatal outcome, have been reported in
patients who received
ZEJULA. In 1902 patients treated with ZEJULA in clinical trials, MDS/AML occurred in 14 patients
(0.7%).
The duration
of therapy with
ZEJULA in patients
who developed secondary MDS/cancer
therapy- related AML varied from <2 months to >4
years. All of these patients
had received previous chemotherapy with platinum
agents and/or other DNA-damaging agents
including radiotherapy. Discontinue ZEJULA if MDS/AML is
confirmed.
5.2 Bone Marrow Suppression
(additions and/or
revisions are underlined)
Hematologic adverse reactions
(thrombocytopenia, anemia and neutropenia) have been
reported in patients treated with ZEJULA.
Grade greater than or equal to 3 thrombocytopenia,
anemia and neutropenia were reported,
respectively, in 29%, 25%,
and 20% of patients
receiving ZEJULA in NOVA. Discontinuation due to thrombocytopenia, anemia, and
neutropenia occurred, respectively,
in 3%, 1%, and 2% of
patients.
Grade greater than or equal to 3 thrombocytopenia, anemia and neutropenia were reported,
respectively, in 28%, 27%, and 13% of
patients receiving ZEJULA in QUADRA. Discontinuation
due to thrombocytopenia, anemia, and
neutropenia occurred, respectively,
in
4%, 2%, and 1% of
patients.
Do not start
ZEJULA until patients
have recovered from hematological
toxicity caused by previous chemotherapy (less than or equal to Grade 1). Monitor
complete blood counts weekly for the first month, monthly
for the next 11 months
of treatment, and periodically after this time.
If hematological
toxicities do not resolve
within 28 days following interruption, discontinue ZEJULA, and refer the
patient to a hematologist for further investigations, including
bone marrow analysis and blood sample for cytogenetics.
5.3 Cardiovascular Effects
(additions and/or
revisions are underlined)
Hypertension and hypertensive crisis
have been reported in
patients treated with ZEJULA. Grade
3-4 hypertension occurred in 9%
of ZEJULA treated patients
compared to 2% of placebo
treated patients in NOVA with a
median time from first dose to first onset of 77 days (range:
4 to 504
days) and with a median duration of 15 days (range:
1 to 86 days).
Discontinuation due to hypertension
occurred in <1%
of
patients. Grade 3-4 hypertension occurred in 5%
of ZEJULA-treated
patients in QUADRA with a median time
from first dose to first
onset of 15 days
(range: 1 to 316 days) and with a
median duration
of 7 days (range: 1 to 118 days).
Discontinuation due to hypertension
occurred in <0.2% of patients.
Monitor blood pressure and heart rate at least weekly for the first two months, then monthly
for the first year
and periodically thereafter during treatment with ZEJULA.
Closely monitor
patients with cardiovascular
disorders, especially coronary insufficiency,
cardiac arrhythmias, and hypertension. Medically manage
hypertension with antihypertensive medications and adjustment
of the ZEJULA dose,
if necessary.
6
Adverse Reactions
6.1 Clinical Trials Experience
(extensive
revisions; please refer to labeling for complete information)
6.2 Postmarketing Experience
(newly added
subsection)
The
following adverse reactions
have been identified during
post-approval use of ZEJULA. 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.
Immune System Disorders:
hypersensitivity (including anaphylaxis)
Nervous System Disorders:
posterior reversible encephalopathy syndrome (PRES)
Psychiatric Disorders: confusional state/disorientation, hallucination
Respiratory, Thoracic,
and Mediastinal Disorders:
non-infectious pneumonitis
Skin and Subcutaneous Tissue Disorders: photosensitivity
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATION
(additions and/or
revisions are underlined)
What is ZEJULA?
ZEJULA
is a prescription medicine used for the:
- maintenance
treatment of adults with ovarian cancer, fallopian tube cancer, or primary peritoneal
cancer, when the cancer comes back. ZEJULA is used after the cancer has responded
(complete or partial response) to treatment with platinum-based chemotherapy.
- treatment of adults with advanced ovarian cancer, fallopian
tube cancer, or primary peritoneal cancer who have been treated with 3 or more
prior types of chemotherapy and who have tumors with:
- a certain “BRCA”
gene mutation, or
- a positive laboratory test, and whose cancer was in response
to treatment with platinum- based chemotherapy, and who have progressed more
than 6 months after the last treatment.
Your
healthcare provider will perform a test to make sure that ZEJULA is right for
you.
It
is not known if ZEJULA is safe and effective in children.
Before taking ZEJULA,
tell your healthcare provider about all of your medical conditions, including
if you:
have
heart problems.
have
high blood pressure.
are
pregnant or plan to become pregnant. ZEJULA can harm your unborn baby and may cause
loss of pregnancy (miscarriage).
If
you are able to become pregnant, your healthcare provider may perform a pregnancy
test before you start treatment with ZEJULA.
Females
who are able to become pregnant should use effective birth control (contraception)
during treatment with ZEJULA and for 6 months after the last dose of ZEJULA. Talk
to your healthcare provider about birth control methods that may be right for
you.
Tell
your healthcare provider right away if you become pregnant.
are
breastfeeding or plan to breastfeed. It is not known if ZEJULA passes into your
breast milk. Do not breastfeed during treatment with ZEJULA and for 1 month
after the last dose of ZEJULA. Talk to your healthcare provider about the best way
to feed your baby during this time.
Tell your healthcare
provider about all the medicines you take, including prescription and over- the-counter
medicines, vitamins, and herbal supplements.
…
What are the possible
side effects of ZEJULA? ZEJULA can cause serious side effects, including:
See “What is the most important information I should know
about ZEJULA?”
The
most common side effects of ZEJULA include:
heart
not beating regularly
changes
in liver function or other blood tests
nausea
pain
in your joints, muscles, and back
constipation
headache
vomiting
dizziness
pain
in the stomach area
change
in the way food tastes
mouth
sores
trouble
sleeping
diarrhea
anxiety
indigestion
or heartburn
sore
throat
dry
mouth
shortness
of breath
tiredness
cough
loss
of appetite
rash
urinary
tract infection
changes in the amount or color of your urine
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