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DESCRIPTION
Neulasta® (pegfilgrastim) is a covalent conjugate of recombinant methionyl
human G-CSF (Filgrastim) and monomethoxypolyethylene glycol. Filgrastim is a water-soluble
175 amino acid protein with a molecular weight of approximately 19 kilodaltons (kD). Filgrastim is
obtained from the bacterial fermentation of a strain of Escherichia coli transformed with a genetically
engineered plasmid containing the human G-CSF gene. To produce pegfilgrastim, a 20 kD monomethoxypolyethylene
glycol molecule is covalently bound to the N-terminal methionyl residue of Filgrastim. The average molecular
weight of pegfilgrastim is approximately 39 kD.
Neulasta® is supplied in 0.6 mL prefilled syringes for subcutaneous injection. Each syringe contains 6 mg pegfilgrastim (based on protein weight), in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.35 mg), sorbitol (30.0 mg), polysorbate 20 (0.02 mg), and sodium (0.02 mg) in water for injection, USP.
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CLINICAL PHARMACOLOGY
Both Filgrastim and pegfilgrastim are Colony Stimulating Factors that act on hematopoietic cells by binding to specific cell surface receptors, thereby stimulating proliferation, differentiation, commitment, and end cell functional activation. Studies on cellular proliferation, receptor binding, and neutrophil function demonstrate that Filgrastim and pegfilgrastim have the same mechanism of action. Pegfilgrastim has reduced renal clearance and prolonged persistence in vivo as compared to Filgrastim.
Pharmacokinetics
The pharmacokinetics and pharmacodynamics of Neulasta® were studied in 379 patients with cancer. The pharmacokinetics of Neulasta® were nonlinear in cancer patients and clearance decreased with increases in dose. Neutrophil receptor binding is an important component of the clearance of Neulasta®, and serum clearance is directly related to the number of neutrophils. For example, the concentration of Neulasta® declined rapidly at the onset of neutrophil recovery that followed myelosuppressive chemotherapy. In addition to numbers of neutrophils, body weight appeared to be a factor. Patients with higher body weights experienced higher systemic exposure to Neulasta® after receiving a dose normalized for body weight. A large variability in the pharmacokinetics of Neulasta® was observed in cancer patients. The half-life of Neulasta® ranged from 15 to 80 hours after subcutaneous injection.
Special Populations
No gender-related differences were observed in the pharmacokinetics of Neulasta®,
and no differences were observed in the pharmacokinetics of geriatric patients
(> 65 years of age) compared to younger patients (< 65 years of age)
(see PRECAUTIONS, Geriatric Use). In a study of 30 patients with varying
degrees of renal dysfunction, including end-stage renal disease, renal dysfunction had no effect on the
pharmacokinetics of pegfilgrastim; thus, dose adjustment in patients with renal dysfunction is not necessary.
The pharmacokinetic profile in pediatric populations or in patients with hepatic insufficiency
has not been assessed.
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CLINICAL STUDIES
Neulasta® was evaluated in three randomized, double blind, controlled studies.
Studies 1 and 2 were active-controlled studies that employed doxorubicin 60 mg/m and docetaxel 75 mg/m administered every 21 days for up to 4 cycles for the
treatment of metastatic breast cancer. Study 1 investigated the utility of a fixed dose of Neulasta®.
Study 2 employed a weight-adjusted dose. In the absence of growth factor support, similar chemotherapy regimens
have been reported to result in a 100% incidence of severe neutropenia (absolute neutrophil count [ANC] < 0.5
x 10/L) with a mean duration of 5-7 days and a 30%-40% incidence of febrile neutropenia.
Based on the correlation between the duration of severe neutropenia and the incidence of febrile
neutropenia found in studies with Filgrastim, duration of severe neutropenia was chosen as the
primary endpoint in both studies, and the efficacy of Neulasta® was demonstrated by
establishing comparability to Filgrastim treated patients in the mean days of severe neutropenia.
In Study 1, 157 patients were randomized to receive a single subcutaneous injection of
Neulasta® 6 mg on day 2 of each chemotherapy cycle or daily subcutaneous Filgrastim 5 mcg/kg/day beginning on
day 2 of each chemotherapy cycle. In Study 2, 310 patients were randomized to receive a single subcutaneous injection of
Neulasta® 100 mcg/kg on day 2 or daily subcutaneous Filgrastim 5 mcg/kg/day beginning on day 2 of
each chemotherapy cycle.
Both studies met the primary objective of demonstrating that the mean days of severe neutropenia of
Neulasta®-treated patients did not exceed that of Filgrastim-treated patients by more
than one day in cycle 1 of chemotherapy (see Table 1). The rates of febrile neutropenia in the two
studies were comparable for Neulasta® and Filgrastim (in the range of 10% to 20%). Other
secondary endpoints included days of severe neutropenia in cycles 2-4, the depth of ANC nadir in
cycles 1-4, and the time to ANC recovery after nadir. In both studies, the results for the secondary
endpoints were similar between the two treatment groups.
Table 1. Mean Days of Severe Neutropenia (in Cycle 1)
| Study |
Mean days of severe neutropenia |
Difference in means
(95% CI) |
| Neulasta® |
Filgrastim
(5 mcg/kg/day) |
Study 1
n = 157 |
1.8 |
1.6 |
0.2
(-0.2, 0.6) |
Study 2
n = 310 |
1.7 |
1.6 |
0.1
(-0.2, 0.4) |
a Study 1 dose = 6 mg x 1; study 2 dose = 100 mcg/kg
x 1
Study 3 was a randomized, double-blind, placebo-controlled study that employed docetaxel 100 mg/m2 administered
every 21 days for up to 4 cycles for the treatment of metastatic or non-metastatic breast cancer. In this study, 928 patients
were randomized to receive a single subcutaneous injection of Neulasta® 6 mg or placebo on day 2 of each chemotherapy cycle.
Study 3 met the primary objective of demonstrating that the incidence of febrile neutropenia (defined as
temperature > 38.2°C and ANC < 0.5 x109/L) was lower for Neulasta®-treated patients
as compared to placebo-treated patients (1% versus 17%, p < 0.001). The incidence of hospitalizations (1% versus 14%)
and IV anti-infective use (2% versus 10%) for the treatment of febrile neutropenia were also lower in the
Neulasta®-treated patients compared with the placebo-treated patients.
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INDICATIONS AND USAGE
Neulasta® is indicated to decrease the incidence of infection,
as manifested by febrile neutropenia, in patients with non-myeloid malignancies
receiving myelosuppressive anti-cancer drugs associated with a clinically significant
incidence of febrile neutropenia (see CLINICAL STUDIES).
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CONTRAINDICATIONS
Neulasta® is contraindicated in patients with known hypersensitivity to pegfilgrastim or Filgrastim.
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WARNINGS
General
The safety and efficacy of Neulasta® for peripheral blood progenitor cell (PBPC) mobilization has not been evaluated in adequate and well-controlled studies. Neulasta® should not be used for PBPC mobilization.
Splenic Rupture
SPLENIC RUPTURE, INCLUDING FATAL CASES, HAS BEEN REPORTED FOLLOWING THE ADMINISTRATION OF NEULASTA® AND ITS PARENT COMPOUND, FILGRASTIM. PATIENTS RECEIVING NEULASTA® WHO REPORT LEFT UPPER ABDOMINAL AND/OR SHOULDER TIP PAIN SHOULD BE EVALUATED FOR AN ENLARGED SPLEEN OR SPLENIC RUPTURE.
Acute Respiratory Distress Syndrome (ARDS)
Acute respiratory distress syndrome (ARDS) has been reported in patients receiving Neulasta®, and is postulated to be secondary to an influx of neutrophils to sites of inflammation in the lungs. Patients receiving Neulasta® who develop fever, lung infiltrates, or respiratory distress should be evaluated for the possibility of ARDS. In the event that ARDS occurs, Neulasta® should be discontinued and/or withheld until resolution of ARDS and patients should receive appropriate medical management for this condition.
Allergic Reactions
Allergic reactions to Neulasta®, manifesting as anaphylaxis, angioedema, or urticaria have been reported in postmarketing experience. The majority of reported events occurred
upon initial exposure. In some cases, symptoms recurred with rechallenge. In rare cases, allergic reactions including anaphylaxis, recurred
within days after initial anti-allergic treatment was discontinued. If a serious allergic
reaction occurs, appropriate therapy should be administered, with close patient follow-up
over several days. Neulasta® should be permanently discontinued in patients with serious
allergic reactions.
Sickle Cell Disorders
Severe sickle cell crises have been associated with the
use of Neulasta® in patients with sickle cell disorders. Severe sickle cell crises,
in some cases resulting in death, have also been associated with Filgrastim, the parent
compound of pegfilgrastim. Only physicians qualified by specialized training or
experience in the treatment of patients with sickle cell disorders should prescribe
Neulasta® for such patients, and only after careful consideration of the potential
risks and benefits.
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PRECAUTIONS
General
Use With Chemotherapy and/or Radiation Therapy
Neulasta® should not be administered in the period between 14
days before and 24 hours after administration of cytotoxic chemotherapy (see
DOSAGE AND ADMINISTRATION) because of
the potential for an increase in sensitivity of rapidly dividing myeloid cells
to cytotoxic chemotherapy.
The use of Neulasta® has not been studied in patients receiving
chemotherapy associated with delayed myelosuppression (eg, nitrosoureas, mitomycin
C).
The administration of Neulasta® concomitantly with 5-fluorouracil
or other antimetabolites has not been evaluated in patients. Administration
of pegfilgrastim at 0, 1, and 3 days before 5-fluorouracil resulted in increased
mortality in mice; administration of pegfilgrastim 24 hours after 5-fluorouracil
did not adversely affect survival.
The use of Neulasta® has not been studied in patients receiving
radiation therapy.
Potential Effect on Malignant Cells
Pegfilgrastim is a growth factor that primarily stimulates neutrophils and neutrophil
precursors; however, the G-CSF receptor through which pegfilgrastim and Filgrastim
act has been found on tumor cell lines, including some myeloid, T-lymphoid,
lung, head and neck, and bladder tumor cell lines. The possibility that pegfilgrastim
can act as a growth factor for any tumor type cannot be excluded. Use of Neulasta®
in myeloid malignancies and myelodysplasia (MDS) has not been studied. In a
randomized study comparing the effects of the parent compound of Neulasta®,
Filgrastim, to placebo in patients undergoing remission induction and consolidation
chemotherapy for acute myeloid leukemia, important differences in remission
rate between the two arms were excluded. Disease-free survival and overall survival
were comparable; however, the study was not designed to detect important differences
in these endpoints.
Information for Patients
Patients should be informed of the possible side effects of Neulasta®
and be instructed to report them to the prescribing physician. Patients should
be informed of the signs and symptoms of allergic drug reactions and be advised
of appropriate actions. Patients should be counseled on the importance of compliance
with their Neulasta® treatment, including regular monitoring
of blood counts.
If it is determined that a patient or caregiver can safely and effectively administer
Neulasta® (pegfilgrastim) at home, appropriate instructions on
the proper use of Neulasta® (pegfilgrastim) should be provided
for patients and their caregivers, including careful review of the "Information
for Patients and Caregivers" insert. Patients and caregivers should be
cautioned against the reuse of needles, syringes, or drug product, and be thoroughly
instructed in their proper disposal. A puncture-resistant container for the
disposal of used syringes and needles should be available.
Laboratory Monitoring
To assess a patient's hematologic status and ability to tolerate myelosuppressive
chemotherapy, a complete blood count and platelet count should be obtained before
chemotherapy is administered. Regular monitoring of hematocrit value and platelet
count is recommended.
Drug Interaction
No formal drug interaction studies between Neulasta® and other
drugs have been performed. Drugs such as lithium may potentiate the release
of neutrophils; patients receiving lithium and Neulasta® should
have more frequent monitoring of neutrophil counts.
Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. This should be considered when interpreting bone-imaging results.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
No mutagenesis studies were conducted with pegfilgrastim. The carcinogenic potential
of pegfilgrastim has not been evaluated in long-term animal studies. In a toxicity
study of 6 months duration in rats given once weekly subcutaneous injections
of up to 1000 mcg/kg of pegfilgrastim (approximately 23-fold higher than the
recommended human dose), no precancerous or cancerous lesions were noted.
When administered once weekly via subcutaneous injections to male and female
rats at doses up to 1000 mcg/kg prior to, and during mating, reproductive performance,
fertility, and sperm assessment parameters were not affected.
Pregnancy Category C
Pegfilgrastim has been shown to have adverse effects in pregnant rabbits when
administered subcutaneously every other day during gestation at doses as low as 50 mcg/kg/dose
(approximately 4-fold higher than the recommended human dose). Decreased maternal
food consumption, accompanied by a decreased maternal body weight gain and decreased
fetal body weights were observed at 50 to 1000 mcg/kg/dose. Pegfilgrastim doses
of 200 and 250 mcg/kg/dose resulted in an increased incidence of abortions.
Increased post-implantation loss due to early resorptions was observed at doses
of 200 to 1000 mcg/kg/dose, and decreased numbers of live rabbit fetuses were
observed at pegfilgrastim doses of 200 to 1000 mcg/kg/dose, given every other
day.
Subcutaneous injections of pegfilgrastim of up to 1000 mcg/kg/dose every other
day during the period of organogenesis in rats were not associated with an embryotoxic
or fetotoxic outcome. However, an increased incidence (compared to historical
controls) of wavy ribs was observed in rat fetuses at 1000 mcg/kg/dose every
other day. Very low levels (<0.5%) of pegfilgrastim crossed the placenta
when administered subcutaneously to pregnant rats every other day during gestation.
Once weekly subcutaneous injections of pegfilgrastim to female rats from day
6 of gestation through day 18 of lactation at doses up to 1000 mcg/kg/dose did
not result in any adverse maternal effects.
There were no deleterious effects on the growth and development of the offspring
and no adverse effects were found upon assessment of fertility indices.
There are no adequate and well-controlled studies in pregnant women. Neulasta®
should be used during pregnancy only if the potential benefit to the mother
justifies the potential risk to the fetus.
Nursing Mothers
It is not known whether pegfilgrastim is excreted in human milk. Because many
drugs are excreted in human milk, caution should be exercised when Neulasta®
is administered to a nursing woman.
Pediatric Use
The safety and effectiveness of Neulasta® in pediatric patients
have not been established. The 6 mg fixed dose single-use syringe formulation
should not be used in infants, children, and smaller adolescents weighing less
than 45 kg.
Geriatric Use
Of the 932 patients with cancer who received Neulasta® in clinical
studies, 139 (15%) were age 65 and over, and 18 (2%) were age 75 and over. No
overall differences in safety or effectiveness were observed between patients
age 65 and older and younger patients.
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ADVERSE REACTIONS
(See WARNINGS, Splenic Rupture, Acute Respiratory Distress Syndrome (ARDS), Allergic Reactions, and Sickle Cell Disorders.)
Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical
trials of Neulasta® cannot be directly compared to rates in the clinical trials of other drugs and may
not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however,
provide a basis for identifying the adverse events that appear to be related to Neulasta® use and for approximating rates.
The data described below reflect exposure to Neulasta® in 932 patients. Neulasta® was studied in placebo- and
active-controlled trials (n = 467, and n = 465, respectively). The population encompassed an age range of 21 to 88 years.
Ninety-two percent of patients were female. The ethnicity of the patients was as follows: 75% Caucasian, 18% Hispanic, 5% Black,
and 1% Asian. Patients with solid tumors (breast [n = 823], lung and thoracic tumors [n = 53]) or lymphoma (n = 56) received
Neulasta® after nonmyeloablative cytotoxic chemotherapy. Most patients received a single 100 mcg/kg (n = 259)
or a single 6 mg (n = 546) dose per chemotherapy cycle over 4 cycles.
In the placebo-controlled trial, bone pain occurred at a higher incidence in Neulasta®-treated patients as compared to
placebo-treated patients. The incidence of other commonly reported adverse events were similar in the Neulasta®- and
placebo-treated patients, and were consistent with the underlying cancer diagnosis and its treatment with chemotherapy.
The data in Table 2 reflect those adverse events occurring in at least 10% of patients treated with Neulasta® in the
placebo-controlled study.
TABLE 2. Adverse Events Occurring in > 10%a of Patients in The Placebo Controlled Study
Event |
Neulasta® (n = 467) |
Placebo (n = 461) |
Alopecia |
48% |
47% |
Bone Painb |
31% |
26% |
Diarrhea |
29% |
28% |
Pyrexia (not including
febrile neutropenia) |
23% |
22% |
Myalgia |
21% |
18% |
Headache |
16% |
14% |
Arthralgia |
16% |
13% |
Vomiting |
13% |
11% |
Asthenia |
13% |
11% |
Peripheral Edema |
12% |
10% |
Constipation |
10% |
6% |
In the active controlled studies, common adverse events occurred at similar rates and severities in both treatment arms
(Neulasta®, n = 465; Filgrastim, n = 331). These adverse experiences occurred at rates between 72% and 15%
and included: nausea, fatigue, alopecia, diarrhea, vomiting, constipation, fever, anorexia, skeletal pain, headache,
taste perversion, dyspepsia, myalgia, insomnia, abdominal pain, arthralgia, generalized weakness, peripheral edema,
dizziness, granulocytopenia, stomatitis, mucositis, and neutropenic fever.
Bone Pain
The analysis of bone pain described below is based on a composite analysis using multiple, related, adverse event terms.
In the placebo-controlled study, the incidence of bone pain was 57% in Neulasta®-treated patients compared
to 50% in placebo-treated patients. Bone pain was generally reported to be of mild-to-moderate severity.
Among patients experiencing bone pain, approximately 37% of Neulasta®- and 31% of placebo-treated patients
utilized non-narcotic analgesics and 10% of Neulasta®- and 9% of placebo-treated patients utilized narcotic analgesics.
In the active-controlled studies, the use of non-narcotic and narcotic analgesics in association with bone pain was similar
between Neulasta®- and Filgrastim-treated patients. No patient withdrew from study due to bone pain.
Laboratory Abnormalities
In clinical studies, leukocytosis (WBC counts > 100 x 109/L) was observed in less than 1% of 932 patients
with non myeloid malignancies receiving Neulasta®. Leukocytosis was not associated with any adverse effects.
Immunogenicity
As with all therapeutic proteins, there is a potential for immunogenicity. Binding antibodies to pegfilgrastim were detected using a BIAcore assay. The approximate limit of detection for this assay is 500 ng/mL. Pre-existing binding antibodies were detected in approximately 6% (51/849) of patients with metastatic breast cancer. Four of 521 pegfilgrastim-treated subjects who were negative at baseline developed binding antibodies to pegfilgrastim following treatment. None of these 4 patients had evidence of neutralizing antibodies detected using a cell-based bioassay.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay, and the observed incidence of antibody positivity in an assay may be influenced by several factors, including sample handling, concomitant medications, and underlying disease. Therefore, comparison of the incidence of antibodies to Neulasta® with the incidence of antibodies to other products may be misleading.
Cytopenias resulting from a neutralizing antibody response to exogenous growth factors have been reported on rare occasions in patients treated with other recombinant growth factors. There is a theoretical possibility that an antibody directed against pegfilgrastim may cross react with endogenous G CSF, resulting in immune-mediated neutropenia. This has not been observed in clinical studies of Neulasta®.
Postmarketing Experience
The following adverse reactions have been identified during postapproval of Neulasta®. 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.
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OVERDOSAGE
The maximum amount of Neulasta® that can be safely administered in single or multiple
doses has not been determined. Single subcutaneous doses of 300 mcg/kg have been administered to
8 healthy volunteers and 3 patients with non small cell lung cancer without serious adverse effects.
These patients experienced a mean maximum ANC of 55 x 109/L, with a corresponding mean maximum
WBC of 67 x 109/L. The absolute maximum ANC observed was 96 x 109/L with a corresponding
absolute maximum WBC observed of 120 x 109/L. The duration of leukocytosis ranged from 6 to 13 days.
Leukapheresis should be considered in the management of symptomatic individuals.
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DOSAGE AND ADMINISTRATION
The recommended dosage of Neulasta® is a single subcutaneous
injection of 6 mg administered once per chemotherapy cycle. Neulasta® should not be administered in the period between 14 days before and 24 hours
after administration of cytotoxic chemotherapy (see PRECAUTIONS).
The 6 mg fixed-dose formulation should not be used in infants, children, and
smaller adolescents weighing less than 45 kg.
No dosing adjustment is necessary for renal dysfunction
(see CLINICAL PHARMACOLOGY, Special Populations).
Neulasta® should be visually inspected for discoloration and
particulate matter before administration. Neulasta® should not
be administered if discoloration or particulates are observed.
For method of administration, please see Information for Patients and Caregivers.
Storage
Neulasta® should be stored refrigerated at 2° to 8°C (36° to
46°F); syringes should be kept in their carton to protect from light until time
of use. Shaking should be avoided. Before injection, Neulasta® may be allowed to reach room temperature for a maximum of 48 hours but should
be protected from light. Neulasta® left at room temperature for
more than 48 hours should be discarded. Freezing should be avoided; however,
if accidentally frozen, Neulasta® should be allowed to thaw in
the refrigerator before administration. If frozen a second time, Neulasta® should be discarded.
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HOW SUPPLIED
Neulasta® is supplied as a preservative-free solution containing
6 mg (0.6 mL) of pegfilgrastim (10 mg/mL) in a single-dose syringe with a 27-gauge, 1/2 inch needle with an UltraSafe® Needle Guard.
The needle cover of the prefilled syringe contains dry natural rubber (a derivative of latex).
Neulasta® is provided in a dispensing pack containing one syringe
(NDC 55513-190-01).
Rx Only
This product, its production, and/or its use may be covered by one or more US Patents, including US Patent Nos. 5,824,784; 4,810,643; 4,999,291; 5,582,823; 5,580,755, as well as other patents or patents pending.
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REFERENCES
| 1. |
Morstyn G, Dexter T, Foote M. Filgrastim (r-metHuG-CSF) in clinical practice. 2nd
ed. 1998;3: 51-71. |
| 2. |
Valerius T, Elsasser D, Repp R, et al. HLA Class-II antibodies recruit G-CSF
activated neutrophils for treatment of B-cell malignancies. Leukemia and Lymphoma. 1997;26: 261-269. |
| 3. |
Heil G, Hoelzer D, Sanz MA, et al. A randomized, double-blind, placebo-controlled,
phase III study of Filgrastim in remission induction and consolidation therapy for adults with de novo Acute
Myeloid Leukemia. Blood. 1997;90: 4710-4718. |
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Manufactured by:
Amgen Manufacturing, Limited, a subsidiary of Amgen Inc.
One Amgen Center Drive
Thousand Oaks, California 91320-1799 U.S.A.
© 2002-2008 Amgen Inc. All rights reserved.
v9 - Issue Date: 04/2008
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This patient package insert provides information and instructions for people
who will be receiving Neulasta® or their caregivers. This patient
package insert does not tell you everything about Neulasta®.
You should discuss any questions you have about treatment with Neulasta®
with your doctor.
What is Neulasta®?
Neulasta® is a man-made form of granulocyte colony-stimulating
factor (G-CSF), which is made using the bacteria E coli. G-CSF is a substance
naturally produced by the body. It stimulates the growth of neutrophils (nu-tro-fils),
a type of white blood cell important in the body's fight against infection.
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What is Neulasta® used
for?
Neulasta® is used to treat neutropenia (nu-tro-peen-ee-ah) that is caused by drugs used to treat cancer. Neutropenia is a condition where the body makes too few neutrophils.
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How does Neulasta® work?
Neulasta® works by helping your body make more neutrophils. To make sure Neulasta® is working, the doctor will ask that the patient have blood tests to count the number of neutrophils. It is important to follow the doctor’s instructions about these tests.
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Who should not take Neulasta®?
Do not take Neulasta® if you have had:
- An allergic reaction to Neulasta® (pegfilgrastim) or any of its ingredients, or to NEUPOGEN® (Filgrastim). See the end of this leaflet for a list of ingredients in Neulasta®.
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What important information do
I need to know about receiving Neulasta®?
Neulasta® can reduce the chance of infection, but it does not prevent all infections. An infection can still happen during the time when your neutrophil levels are low. You must be alert and look for some of the common signs or symptoms of infection, such as fever, chills, rash, sore throat, diarrhea, or redness, swelling, or pain around a cut or sore. If you notice any of these signs or symptoms during treatment with Neulasta®, tell your doctor or nurse immediately.
Occasionally pain and redness may occur at the injection site. If there is a lump, swelling, or bruising at the injection site that does not go away, talk to the doctor.
If you have a sickle cell disorder, make sure that your doctor knows about it before using Neulasta®. If you have a sickle cell crisis after getting Neulasta®, tell your doctor right away.
Make sure your doctor knows about all medicines and all herbal and vitamin supplements you are taking before starting Neulasta®. If you are taking lithium, you may need more frequent blood tests.
The doctor, nurse, or caregiver will usually inject the dose of Neulasta® a day after the last dose of chemotherapy in each cycle. Neulasta® should only be injected on the day the doctor has determined and should not be injected until approximately 24 hours after receiving chemotherapy.
More information about Neulasta® is available in the Physician Package Insert. If you have any questions, talk to your doctor.
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What are possible serious side effects of Neulasta®?
- Spleen Rupture. Your spleen may become enlarged and can rupture while taking Neulasta®. A ruptured spleen can cause death. The spleen is located in the upper left section of your stomach area. Call your doctor right away if you have pain in the left upper stomach area or left shoulder tip area. This pain could mean your spleen is enlarged or ruptured.
- Serious Allergic Reactions. Neulasta®can cause serious allergic reactions. These reactions can cause shortness of breath, wheezing, dizziness, swelling around the mouth or eyes, fast pulse, sweating, and hives. If you start to have any of these symptoms, call your doctor or seek emergency care right away. If you have an allergic reaction during the injection of Neulasta â , stop the injection. Call your doctor right away.
- A serious lung problem called acute respiratory distress syndrome (ARDS). Call your doctor or seek emergency care right away if you have shortness of breath, trouble breathing or a fast rate of breathing.
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What are the most common side effects of Neulasta®?
The most common side effect you may experience is aching in the bones and muscles. If this happens, it can usually be relieved with a non-aspirin pain reliever, such as acetaminophen.
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What about pregnancy
or breastfeeding?
Neulasta® has not been studied in pregnant women, and its effects
on unborn babies are not known. If you take Neulasta® while you
are pregnant, it is possible that small amounts of it may get into your baby's
blood. It is not known if Neulasta® can get into human breast
milk. If you are pregnant, plan to become pregnant, think you may be pregnant,
or are breastfeeding, you should tell your doctor before using Neulasta®.
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HOW TO PREPARE AND GIVE A
Neulasta® INJECTION
Neulasta® is provided in a prefilled syringe. Neulasta®
should be stored in its carton to protect from light until use. If you are
giving someone else Neulasta® injections, it is important that
you know how to inject Neulasta®. Before getting your Neulasta® injection, always check to see that:
- The name Neulasta® appears on the carton and prefilled syringe
label.
- The expiration date on the prefilled syringe has not passed. You should
not use a prefilled syringe after the date on the label.
- The Neulasta® liquid should always be clear and colorless.
Do not use Neulasta® if the contents of the prefilled syringe
appear discolored or cloudy, or if the prefilled syringe appears to contain
lumps, flakes, or particles.
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IMPORTANT: TO HELP AVOID POSSIBLE INFECTION, YOU SHOULD FOLLOW THESE INSTRUCTIONS.
Setting up for an injection
 |
|
| 1. |
Find a clean, flat working surface, such as a table.
|
| 2. |
Remove the carton containing the prefilled syringe of Neulasta® from the
refrigerator. Allow Neulasta® to reach room temperature (this takes about 30 minutes).
Remove the syringe from the carton before injection. Each prefilled syringe should be used
only once. DO NOT SHAKE THE PREFILLED SYRINGE. Shaking may damage Neulasta®. If the
prefilled syringe has been shaken vigorously, the solution may appear foamy and it
should not be used.
|
| 3. |
Assemble the supplies you will need for an injection:
|
|
- Neulasta® prefilled syringe with transparent (clear)
plastic blue needle guard attached
- An alcohol swab and a cotton ball or gauze
- puncture-proof disposal container
|
| 4. |
Wash your hands with soap and warm water.
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HOW TO PREPARE FOR INJECTION OF Neulasta®
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| 5. |
Remove the syringe from the package and the tray.
Check to see that the plastic blue needle guard is covering the barrel of the
glass syringe. DO NOT push the blue needle guard over the needle cover before
injection. This may activate or lock the needle guard. If the blue needle
guard is covering the needle that means it has been activated. Do NOT use
that syringe. Dispose of that syringe in the puncture-proof disposal
container. Use a new syringe. Do not activate the needle guard prior
to injection.
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| 6. |
Hold the syringe barrel through the needle guard windows with the
needle pointing up. Holding the syringe with the needle pointing up helps to
prevent medicine from leaking out of the needle. Carefully pull the needle
cover straight off.
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| 7. |
Check the syringe for air bubbles. If there are air bubbles,
gently tap the syringe with your fingers until the air bubbles rise to the top of the
syringe. Slowly push the plunger up to force the air bubbles out of the syringe.
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| 8 |
Gently place the prefilled syringe with the window flat on your clean
working surface so that the needle does not touch anything.
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Selecting and preparing the injection site
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| 9. |
Choose an injection site. Four recommended
injection sites for Neulasta® are:
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- The outer area of the upper arms
- The abdomen, except for the two inch area around the navel
- The front of the middle thighs
- The upper outer areas of the buttocks
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| 10. |
Clean the injection site with an alcohol swab.
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Injecting the dose of Neulasta®
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| 11. |
Pick up the prefilled syringe from your clean
flat working surface by grabbing the sides of the needle guard with
your thumb and forefinger.
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| 12. |
Hold the syringe in the hand you will use to
inject Neulasta®. Use the other hand to pinch a fold of
skin at the cleaned injection site. Note: Hold the syringe barrel
through the needle guard windows when giving the injection.
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| 13. |
Holding the syringe like a pencil, use a quick
"dart-like" motion to insert the needle either straight up and down
(90 degree angle) or at a slight angle (45 degrees) into the skin.
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| 14. |
After the needle is inserted, let go of the skin.
Pull the plunger back slightly. If no blood appears, slowly push down on
the plunger all the way, until all the Neulasta® is injected.
If blood comes into the syringe, do not inject Neulasta®,
because the needle has entered a blood vessel. Withdraw the syringe
and discard it in the puncture-proof container. Repeat the steps to
prepare a new prefilled syringe and choose and clean a new injection site.
Remember to check again for blood before injecting Neulasta®.
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| 15. |
When the syringe is empty, pull the needle out of the skin
and place a cotton ball or gauze over the injection site and press for several seconds.
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| 16. |
Use a prefilled syringe with the needle guard only once.
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Activating the Needle Guard after the injection has been given
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| 17. |
After injecting Neulasta® from the
prefilled syringe, do not recap the needle. Keep your hands behind the needle at
all times. While holding the clear plastic finger grip of the syringe with one
hand, grasp the blue needle guard with your free hand and slide the blue needle
guard over the needle until the needle is completely covered and the needle
guard clicks into place. NOTE: If an audible click is not heard, the needle
guard may not be completely activated.
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| 18. |
Place the prefilled syringe with the activated needle guard
into a puncture-proof container for proper disposal as described below.
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Disposal of prefilled syringes and needle guards
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You should always follow the instructions given
by your doctor, nurse, or pharmacist on how to properly dispose of
containers with used syringes and needle guards. There may be
special state and local laws for disposal of used needles and
syringes.
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- Do not throw the container in the household trash. Do not recycle.
- DO NOT put the needle cover (the cap) back on the needle.
- Place all used needle covers and syringes in a hard-plastic container
with a screw-on cap, or a metal container with a plastic lid, such as a coffee
can, labeled "used syringes". If a metal container is used, cut a small hole
in the plastic lid and tape the lid to the metal container. If a
hard-plastic container is used, always screw the cap on tightly after
each use.
- Do not use glass or clear plastic containers.
- When the container is full, tape around the cap or lid to make sure the cap or lid does not come off.
- Always keep the container out of the reach of children.
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How should Neulasta® be stored?
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Neulasta® should be stored
in the refrigerator at 2° to 8° C (36° to 46° F), but not in the freezer.
Neulasta® should be protected from light, so you should keep
it in its carton until you are ready to use it. Avoid shaking
Neulasta®. If Neulasta® is accidentally
frozen, allow it to thaw in the refrigerator before injecting.
However, if it is frozen a second time, do not use. Neulasta®
can be left out at room temperature for up to 48 hours. Do not
leave Neulasta® in direct sunlight.
For all questions about storage, contact your doctor, nurse,
or pharmacist.
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What are the ingredients in Neulasta® ?
Each syringe contains pegfilgrastim in a sterile, clear, colorless, preservative free solution containing acetate, sorbitol, polysorbate 20, and sodium.
The needle cover on the single-use prefilled syringe contains dry natural rubber
(latex), which should not be handled by persons sensitive to this substance.
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Manufactured by:
Amgen Manufacturing, Limited,
a subsidiary of Amgen Inc.
One Amgen Center Drive
Thousand Oaks, California 91320-1799
© 2002-2008 Amgen Inc. All rights reserved.
v6 - Issue Date: 04/2008
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