Home' The Source : Second Quarter 2015 Contents BRIEF SUMMARY OF PRESCRIBING INFORMATION FOR
GRANIX (tbo-filgrastim) injection, for subcutaneous use
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1 INDICATIONS AND USAGE
GRANIX is indicated to reduce the duration of severe neutropenia in patients
with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs
associated with a clinically significant incidence of febrile neutropenia.
5 WARNINGS AND PRECAUTIONS
5.1 Splenic Rupture
Splenic rupture, including fatal cases, can occur following administration of
human granulocyte colony-stimulating factors. In patients who report upper
abdominal or shoulder pain after receiving GRANIX, discontinue GRANIX and
evaluate for an enlarged spleen or splenic rupture.
5.2 Acute Respiratory Distress Syndrome (ARDS)
Acute respiratory distress syndrome (ARDS) can occur in patients receiving
human granulocyte colony-stimulating factors. Evaluate patients who develop
fever and lung infiltrates or respiratory distress after receiving GRANIX, for
ARDS. Discontinue GRANIX in patients with ARDS.
5.3 Allergic Reactions
Serious allergic reactions including anaphylaxis can occur in patients receiv-
ing human granulocyte colony-stimulating factors. Reactions can occur on
initial exposure. The administration of antihistamines' steroids' bronchodi-
lators' and/or epinephrine may reduce the severity of the reactions. Perma-
nently discontinue GRANIX in patients with serious allergic reactions. Do not
administer GRANIX to patients with a history of serious allergic reactions to
filgrastim or pegfilgrastim.
5.4 Use in Patients with Sickle Cell Disease
Severe and sometimes fatal sickle cell crises can occur in patients with sickle
cell disease receiving human granulocyte colony-stimulating factors. Consider
the potential risks and benefits prior to the administration of human granulo-
cyte colony-stimulating factors in patients with sickle cell disease. Discontinue
GRANIX in patients undergoing a sickle cell crisis.
5.5 Capillary Leak Syndrome
Capillary leak syndrome (CLS) can occur in patients receiving human granulo-
cyte colony-stimulating factors and is characterized by hypotension, hypoalbu-
minemia, edema and hemoconcentration. Episodes vary in frequency, sever-
ity and may be life-threatening if treatment is delayed. Patients who develop
symptoms of capillary leak syndrome should be closely monitored and receive
standard symptomatic treatment, which may include a need for intensive care.
5.6 Potential for Tumor Growth Stimulatory Effects on Malignant Cells
The granulocyte colony-stimulating factor (G-CSF) receptor through which
GRANIX acts has been found on tumor cell lines. The possibility that GRANIX
acts as a growth factor for any tumor type, including myeloid malignancies and
myelodysplasia, diseases for which GRANIX is not approved, cannot be excluded.
6 ADVERSE REACTIONS
The following potential serious adverse reactions are discussed in greater
detail in other sections of the labeling:
see Warnings and Precautions (5.1)]
see Warnings and Precautions (5.2)]
see Warnings and Precautions (5.3)]
see Warnings and Precautions (5.4)]
[see Warnings and Precautions (5.5)]
Warnings and Precautions (5.6)]
The most common treatment-emergent adverse reaction that occurred at an
incidence of at least 1% or greater in patients treated with GRANIX at the
recommended dose and was numerically two times more frequent than in the
placebo group was bone pain.
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 com-
pared to rates in the clinical trials of another drug and may not reflect the rates
observed in clinical practice.
GRANIX clinical trials safety data are based upon the results of three randomized
clinical trials in patients receiving myeloablative chemotherapy for breast can-
cer (N=348), lung cancer (N=240) and non-Hodgkin's lymphoma (N=92). In the
breast cancer study, 99% of patients were female, the median age was 50 years,
and 86% of patients were Caucasian. In the lung cancer study, 80% of patients
were male, the median age was 58 years, and 95% of patients were Caucasian. In
the non-Hodgkin's lymphoma study, 52% of patients were male, the median age
was 55 years, and 88% of patients were Caucasian. In all three studies a placebo
(Cycle 1 of the breast cancer study only) or a non-US-approved filgrastim prod-
uct were used as controls. Both GRANIX and the non-US-approved filgrastim
product were administered at 5 mcg/kg subcutaneously once daily beginning
one day after chemotherapy for at least five days and continued to a maximum
of 14 days or until an ANC of 10,000 x 106/L after nadir was reached.
Bone pain was the most frequent treatment-emergent adverse reaction that
occurred in at least 1% or greater in patients treated with GRANIX at the recom-
mended dose and was numerically two times more frequent than in the placebo
group. The overall incidence of bone pain in Cycle 1 of treatment was 3.4%
(3.4% GRANIX, 1.4% placebo, 7.5% non-US-approved filgrastim product).
In clinical studies, leukocytosis (WBC counts > 100,000 x 106/L) was observed
in less than 1% patients with non-myeloid malignancies receiving GRANIX. No
complications attributable to leukocytosis were reported in clinical studies.
Additional Adverse Reactions
Other adverse reactions known to occur following administration of human
granulocyte colony-stimulating factors include myalgia, headache, vomiting,
Sweet's syndrome (acute febrile neutrophilic dermatosis), cutaneous vascu-
litis and thrombocytopenia.
As with all therapeutic proteins, there is a potential for immunogenicity. The
incidence of antibody development in patients receiving GRANIX has not been
7 DRUG INTERACTIONS
No formal drug interaction studies between GRANIX and other drugs have
Drugs which may potentiate the release of neutrophils' such as lithium'
should be used with caution.
Increased hematopoietic activity of the bone marrow in response to growth fac-
tor therapy has been associated with transient positive bone imaging changes.
This should be considered when interpreting bone-imaging results.
8 USE IN SPECIFIC POPULATIONS
Pregnancy Category C
There are no adequate and well-controlled studies of GRANIX in pregnant
women. In animal reproduction studies, treatment of pregnant rabbits with
tbo-filgrastim resulted in increased spontaneous abortion and fetal malforma-
tions at systemic exposures substantially higher than the human exposure.
GRANIX should be used during pregnancy only if the potential benefit justifies
the potential risk to the fetus.
In an embryofetal developmental study, pregnant rabbits were administered
subcutaneous doses of tbo-filgrastim during the period of organogenesis
at 1, 10 and 100 mcg/kg/day. Increased abortions were evident in rabbits
treated with tbo-filgrastim at 100 mcg/kg/day. This dose was maternally toxic
as demonstrated by reduced body weight. Other embryofetal findings at this
dose level consisted of post-implantation loss' decrease in mean live litter size
and fetal weight, and fetal malformations such as malformed hindlimbs and
cleft palate. The dose of 100 mcg/kg/day corresponds to a systemic expo-
sure (AUC) of approximately 50-90 times the exposures observed in patients
treated with the clinical tbo-filgrastim dose of 5 mcg/kg/day.
8.3 Nursing Mothers
It is not known whether tbo-filgrastim is secreted in human milk. Because many
drugs are excreted in human milk, caution should be exercised when GRANIX
is administered to a nursing woman. Other recombinant G-CSF products are
poorly secreted in breast milk and G-CSF is not orally absorbed by neonates.
8.4 Pediatric Use
The safety and effectiveness of GRANIX in pediatric patients have not been
8.5 Geriatric Use
Among 677 cancer patients enrolled in clinical trials of GRANIX, a total of 111
patients were 65 years of age and older. No overall differences in safety or effec-
tiveness were observed between patients age 65 and older and younger patients.
8.6 Renal Impairment
The safety and efficacy of GRANIX have not been studied in patients with
moderate or severe renal impairment. No dose adjustment is recommended
for patients with mild renal impairment.
8.7 Hepatic Impairment
The safety and efficacy of GRANIX have not been studied in patients with
No case of overdose has been reported.
©2014 Cephalon, Inc., a wholly-owned subsidiary of Teva Pharmaceutical
Industries Ltd. All rights reserved.
GRANIX is a registered trademark of Teva Pharmaceutical Industries Ltd.
Sicor Biotech UAB
Teva Pharmaceuticals USA, Inc.
North Wales, PA 19454
U.S. License No. 1803
Product of Israel
GRX-40502 December 2014
This brief summary is based on TBO-004 GRANIX full Prescribing Information.
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