Approved Drug Label (PDF)
6
Adverse Reactions
6.2 Postmarketing Experience
(Additions and/or revisions underlined)
The following adverse reactions have been
identified during post-approval use of filgrastim products. 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.
- splenic rupture
and splenomegaly (enlarged spleen) [see Warnings
and Precautions (5.1)]
- acute respiratory distress syndrome [see
Warnings and Precautions (5.2)]
- anaphylaxis [see
Warnings and Precautions (5.3)]
- sickle cell disorders [see
Warnings and Precautions (5.4)]
- glomerulonephritis [see Warnings and Precautions (5.5)]
- alveolar hemorrhage and hemoptysis [see
Warnings and Precautions (5.6)]
- capillary leak syndrome [see
Warnings and Precautions (5.7)]
- leukocytosis [see
Warnings and Precautions (5.10)]
- cutaneous vasculitis [see Warnings and Precautions (5.11)]
- Sweet’s syndrome
(acute febrile neutrophilic dermatosis)
- decreased bone density and osteoporosis in pediatric patients
receiving chronic treatment with filgrastim products.
- myelodysplastic syndrome
(MDS) and acute
myeloid leukemia (AML) in patients
with breast and lung cancer receiving chemotherapy and/or radiotherapy [see Warnings and Precautions (5.8)]
- aortitis [see
Warnings and Precautions (5.15)]
- extramedullary hematopoiesis
Approved Drug Label (PDF)
5
Warnings and Precautions
5.8 Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)
(Subsection title
revised; Additions and/or revisions underlined)
Patients with Severe Chronic Neutropenia
Confirm the diagnosis of SCN before initiating
NIVESTYM therapy.
MDS and AML have been reported to occur in the natural
history of congenital neutropenia without cytokine therapy. Cytogenetic
abnormalities, transformation to MDS, and AML have also been observed in patients
treated with filgrastim products for SCN. Based on available data including a postmarketing
surveillance study, the risk of developing MDS and AML appears to be confined
to the subset of patients with congenital neutropenia. Abnormal cytogenetics
and MDS have been associated with the eventual development of myeloid leukemia.
The effect of filgrastim products on the development of abnormal cytogenetics
and the effect of continued filgrastim products administration in patients with
abnormal cytogenetics or MDS are unknown. Monitor patients for signs and
symptoms of MDS/AML in these settings. If a patient with SCN develops
abnormal cytogenetics or myelodysplasia‚ the risks and benefits of continuing
NIVESTYM should be carefully considered.
Patients with Breast and Lung Cancer
MDS and AML have been associated with the use of
filgrastim products in conjunction with chemotherapy and/or radiotherapy in
patients with breast and lung cancer. Monitor patients for signs and symptoms
of MDS/AML in these settings.
6
Adverse Reactions
(Addition of the
following to the bulleted line listing)
6.3 Postmarketing Experience
(Additions and/or
revisions underlined)
The following adverse reactions have been identified
during post-approval use of filgrastim products. 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.
splenic rupture and splenomegaly (enlarged spleen) [see Warnings and Precautions (5.1)]
acute respiratory distress syndrome [see Warnings and Precautions (5.2)]
anaphylaxis [see
Warnings and Precautions (5.3)]
sickle cell disorders [see Warnings and Precautions (5.4)]
glomerulonephritis [see Warnings and Precautions (5.5)]
alveolar hemorrhage and hemoptysis [see Warnings and Precautions (5.6)]
capillary leak syndrome [see Warnings and Precautions (5.7)]
leukocytosis [see
Warnings and Precautions (5.10)]
cutaneous vasculitis [see Warnings and Precautions (5.11)]
Sweet’s syndrome (acute febrile neutrophilic dermatosis)
decreased bone density and osteoporosis in pediatric
patients receiving chronic treatment with filgrastim products.
myelodysplastic syndrome
(MDS) and acute myeloid leukemia (AML) in patients with breast and lung cancer
receiving chemotherapy and/or radiotherapy [see
Warnings and Precautions (5.8)]
aortitis [see Warnings and Precautions (5.15)]
8
Use in Specific Populations
8.1 Pregnancy
(Additions and/or
revisions underlined)
Risk
Summary
Available
data from published studies, including several observational studies of
pregnancy outcomes in women exposed to filgrastim products and those who were
unexposed, have not established an association with filgrastim products use during
pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes
(see Data). Reports in the scientific
literature have described transplacental passage of filgrastim in pregnant women
when administered less than or equal to 30 hours prior to preterm delivery (less
than or equal to 30 weeks gestation). In animal reproduction studies, effects
of filgrastim on prenatal development have been studied in rats and rabbits. No
malformations were observed in either species. No maternal or fetal effects
were observed in pregnant rats at doses up to 58 times the human doses.
Filgrastim has been shown to have adverse effects in pregnant rabbits at
doses 2 to 10 times higher than the human doses (see Data).
The
estimated background risk of major birth defects and miscarriage for the
indicated populations is unknown. All pregnancies have a background risk of
birth defect, loss, or other adverse outcomes. In the U.S. general population,
the estimated background risks of major birth defects and miscarriage in
clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Data
Human data
Several
observational studies based on the Severe Chronic Neutropenia International
Registry (SCNIR) described pregnancy outcomes in women with severe chronic
neutropenia (SCN) who were exposed to filgrastim products during pregnancy and women
with SCN who were unexposed. No major differences were seen between treated and
untreated women with respect to pregnancy outcome (including miscarriage and preterm
labor), newborn complications (including birth weight) and infections.
Methodological limitations of these studies, include small sample size, and
lack of generalizability due to the underlying maternal condition.
Animal data
Effects
of filgrastim on prenatal development have been studied in rats and rabbits. No
malformations were observed in either species. Filgrastim has been shown to have
adverse effects in pregnant rabbits at doses 2 to 10 times higher than the
human doses. In pregnant rabbits showing signs of maternal toxicity, reduced
embryo-fetal survival (at 20 and 80 mcg/kg/day) and increased abortions (at 80
mcg/kg/day) were observed. In pregnant rats, no maternal or fetal effects were
observed at doses up to 575 mcg/kg/day, which is approximately 58 times higher
than the human dose of 10 mcg/kg/day.
Offspring
of rats administered filgrastim during the peri-natal and lactation periods exhibited
a delay in external differentiation and growth retardation (greater than or equal
to 20 mcg/kg/day) and slightly reduced survival rate (100 mcg/kg/day).
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
(Additions and/or
revisions underlined)
Advise
the patient to read the FDA-approved patient labeling (Patient Information and
Instructions for Use). Review the steps for direct patient administration with
patients and caregivers. Training by the healthcare provider should aim to
ensure that patients and caregivers can successfully perform all of the steps
in the Instructions for Use of NIVESTYM vial and prefilled syringe, including
showing the patient or caregiver how to measure the required dose, particularly
if a patient is on a dose other than the entire prefilled syringe. If a patient
or caregiver is not able to demonstrate that they can measure the dose and
administer the product successfully, you should consider whether the patient is
an appropriate candidate for self-administration of NIVESTYM or whether the
patient would benefit from a different NIVESTYM presentation. Advise patients
of the following risks and potential risks with NIVESTYM:
Rupture
or enlargement of the spleen may occur. Symptoms include left upper quadrant
abdominal pain or left shoulder pain. Advise patients to report pain in these areas
to their physician immediately [see
Warnings and Precautions (5.1)].
Dyspnea,
with or without fever, progressing to Acute Respiratory Distress Syndrome, may
occur.
Advise patients to report dyspnea to their
physician immediately [see Warnings and
Precautions (5.2)].
Serious
allergic reactions may occur, which may be signaled by rash‚ facial edema‚
wheezing‚ dyspnea‚ hypotension‚ or tachycardia. Advise patients to seek
immediate medical attention if signs or symptoms of hypersensitivity reaction occur
[see Warnings and Precautions (5.3)].
In
patients with sickle cell disease, sickle cell crisis and death have occurred. Discuss
potential risks and benefits for patients with sickle cell disease prior to the
administration of human granulocyte colony-stimulating factors [see Warnings and Precautions (5.4)].
Glomerulonephritis
may occur. Symptoms include swelling of the face or ankles, dark colored urine
or blood in the urine, or a decrease in urine production. Advise patients to
report signs or symptoms of glomerulonephritis to their physician immediately [see Warnings and Precautions (5.5)].
There may be an increased risk of Myelodysplastic
Syndrome and/or Acute Myeloid Leukemia in patients with congenital neutropenia
who receive filgrastim products and in patients with breast and lung cancer who
receive filgrastim products in conjunction with chemotherapy and/or radiation
therapy. Symptoms of MDS and AML may include tiredness, fever, and easy
bruising or bleeding. Advise patients to report to their physician signs and
symptoms of MDS/AML [see Warnings and
Precautions (5.8)].
Cutaneous
vasculitis may occur, which may be signaled by purpura or erythema. Advise
patients to report signs or symptoms of vasculitis to their physician
immediately [see Warnings and Precautions
(5.11)].
Aortitis
may occur. Symptoms may include fever, abdominal pain, malaise, back pain, and increased
inflammatory markers. Advise patients to report signs and symptoms of aortitis
to their physician immediately [see
Warnings and Precautions (5.15)].
Instruct
patients who self-administer NIVESTYM using the prefilled syringe or
single-dose vial of the:
Importance
of following the applicable Instructions for Use.
Dangers
of reusing needles, syringes, or unused portions of single-dose vials.
Importance
of following local requirements for proper disposal of used syringes, needles,
and unused vials.
Importance
of informing the healthcare provider if difficulty occurs when measuring or
administering partial contents of the NIVESTYM prefilled syringe. If difficulty
occurs, use of the NIVESTYM vial may be considered.
Difference
in product concentration of the NIVESTYM prefilled syringe in comparison to the
NIVESTYM vial. When switching patients from the NIVESTYM prefilled syringe to
the NIVESTYM vial, or vice versa, ensure that patients understand the correct
volume to be administered since the concentration of NIVESTYM differs between
the prefilled syringe and the vial.
PATIENT INFORMATION
(Additions and/or
revisions underlined)
…
- Call your
healthcare provider if you develop any of these symptoms during treatment with
NIVESTYM.
…
The
most common side effects experienced in patients receiving NIVESTYM include:
Patients with cancer receiving chemotherapy: fever,
pain, rash, cough, and shortness of breath
Patients with acute myeloid leukemia receiving
chemotherapy: pain, nose bleed, and rash
Patients with cancer receiving chemotherapy followed
by bone marrow transplant: rash
Patients who are having their own blood cells
collected: bone pain, fever, and headache
- Patients with severe chronic neutropenia: pain,
decreased red blood cells, nose bleed, diarrhea, reduced sensation, and hair loss
…
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