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Neulasta

Last reviewed on RxList: 5/9/2016
Drug Description

NEULASTA®
(pegfilgrastim) Injection

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 E 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 provided in two presentations:

  • Neulasta for manual subcutaneous injection is supplied in 0.6 mL prefilled syringes. The prefilled syringe does not bear graduation marks and is designed to deliver the entire contents of the syringe (6 mg/0.6 mL).
  • On-body Injector for Neulasta is supplied with a prefilled syringe containing 0.64 mL of Neulasta in solution that delivers 0.6 mL of Neulasta in solution when used with the On-body Injector for Neulasta. The syringe does not bear graduation marks and is only to be used with the On-body Injector for Neulasta.

The delivered 0.6 mL dose from either the prefilled syringe for manual subcutaneous injection or the On-body Injector for Neulasta contains 6 mg pegfilgrastim (based on protein weight) in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.35 mg), polysorbate 20 (0.02 mg), sodium (0.02 mg), and sorbitol (30 mg) in Water for Injection, USP.

For Consumers

What are the possible side effects of pegfilgrastim (Neulasta)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using pegfilgrastim and call your doctor at once if you have a serious side effect such as:

  • sudden or severe pain in your left upper stomach spreading up to your shoulder;
  • severe dizziness, skin rash, or flushing (warmth, redness, or tingly feeling);
  • rapid breathing or feeling short of breath;
  • signs of infection such as fever, chills, sore throat, flu symptoms, easy bruising or...
Indications & Dosage

INDICATIONS

Patients With Cancer Receiving Myelosuppressive Chemotherapy

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].

Neulasta is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

Patients With Hematopoietic Subsyndrome Of Acute Radiation Syndrome

Neulasta is indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation [see DOSAGE AND ADMINISTRATION and Clinical Studies].

DOSAGE AND ADMINISTRATION

Patients With Cancer Receiving Myelosuppressive Chemotherapy

The recommended dosage of Neulasta is a single subcutaneous injection of 6 mg administered once per chemotherapy cycle. For dosing in pediatric patients weighing less than 45 kg, refer to Table 1. Do not administer Neulasta between 14 days before and 24 hours after administration of cytotoxic chemotherapy.

Patients With Hematopoietic Subsyndrome Of Acute Radiation Syndrome

The recommended dose of Neulasta is two doses, 6 mg each, administered subcutaneously one week apart. For dosing in pediatric patients weighing less than 45 kg, refer to Table 1. Administer the first dose as soon as possible after suspected or confirmed exposure to radiation levels greater than 2 gray (Gy). Administer the second dose one week after the first dose.

Obtain a baseline complete blood count (CBC). Do not delay administration of Neulasta if a CBC is not readily available. Estimate a patient's absorbed radiation dose (i.e., level of radiation exposure) based on information from public health authorities, biodosimetry if available, or clinical findings such as time to onset of vomiting or lymphocyte depletion kinetics.

Administration

Neulasta is administered subcutaneously via a single prefilled syringe for manual use or for use with the On-body Injector for Neulasta which is co-packaged with a single prefilled syringe. Use of the On-body Injector for Neulasta is not recommended for patients with Hematopoietic Subsyndrome of Acute Radiation Syndrome. Use of the On-body Injector for Neulasta has not been studied in pediatric patients.

Prior to use‚ remove the carton from the refrigerator and allow the Neulasta prefilled syringe to reach room temperature for a minimum of 30 minutes. Discard any prefilled syringe left at room temperature for greater than 48 hours.

Visually inspect parenteral drug products (prefilled syringe) for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer Neulasta if discoloration or particulates are observed.

The needle cap on the prefilled syringes contains dry natural rubber (derived from latex); persons with latex allergies should not administer these products.

Pediatric Patients Weighing Less Than 45 kg

The Neulasta prefilled syringe is not designed to allow for direct administration of doses less than 0.6 mL (6 mg). The syringe does not bear graduation marks which are necessary to accurately measure doses of Neulasta less than 0.6 mL (6 mg) for direct administration to patients. Thus, the direct administration to patients requiring dosing of less than 0.6 mL (6 mg) is not recommended due to the potential for dosing errors. Refer to Table 1.

Table 1: Dosing of Neulasta for pediatric patients weighing less than 45 kg

Body Weight Neulasta Dose Volume to Administer
Less than 10 kg* See below* See below*
10 - 20 kg 1.5 mg 0.15 mL
21 -30 kg 2.5 mg 0.25 mL
31 -44 kg 4 mg 0.4 mL
*For pediatric patients weighing less than 10 kg, administer 0.1 mg/kg (0.01 mL/kg) of Neulasta.

Special Healthcare Provider Instructions For The On-body Injector For Neulasta

A healthcare provider must fill the On-body Injector with Neulasta using the prefilled syringe and then apply the On-body Injector for Neulasta to the patient's skin (abdomen or back of arm). The back of the arm may only be used if there is a caregiver available to monitor the status of the On-body Injector for Neulasta. Approximately 27 hours after the On-body Injector for Neulasta is applied to the patient's skin, Neulasta will be delivered over approximately 45 minutes. A healthcare provider may initiate administration with the On-body Injector for Neulasta on the same day as the administration of cytotoxic chemotherapy, as long as the On-body Injector for Neulasta delivers Neulasta no less than 24 hours after administration of cytotoxic chemotherapy.

The prefilled syringe co-packaged in Neulasta Onpro™ kit must only be used with the On-body Injector for Neulasta. The prefilled syringe contains additional solution to compensate for liquid loss during delivery through the On-body Injector for Neulasta. If the prefilled syringe co-packaged in Neulasta Onpro kit is used for manual subcutaneous injection, the patient will receive an overdose. If the single-dose prefilled syringe for manual use is used with the On-body Injector for Neulasta, the patient may receive less than the recommended dose.

Do not use the On-body Injector for Neulasta to deliver any other drug product except the Neulasta prefilled syringe co-packaged with the On-body Injector for Neulasta.

The On-body Injector for Neulasta should be applied to intact, non-irritated skin on the arm or abdomen.

A missed dose could occur due to an On-body Injector for Neulasta failure or leakage. If the patient misses a dose, a new dose should be administered by single prefilled syringe for manual use, as soon as possible after detection.

Refer to the Healthcare Provider Instructions for Use for the On-body Injector for Neulasta for full administration information.

Advice To Give To Patients Regarding Administration Via The On-body Injector For Neulasta

Advise patients to avoid activities such as traveling, driving, or operating heavy machinery during hours 26-29 following application of the On-body Injector for Neulasta (this includes the 45-minute delivery period plus an hour post-delivery). Patients should have a caregiver nearby for the first use.

Refer the patient to the dose delivery information written on the Patient Instructions for Use. Provide training to patients to ensure they understand when the dose delivery of Neulasta will begin and how to monitor the On-body Injector for Neulasta for completed delivery. Ensure patients understand how to identify signs of malfunction of On-body Injector for Neulasta [see WARNINGS AND PRECAUTIONS and PATIENT INFORMATION].

HOW SUPPLIED

Dosage Forms And Strengths

  • Injection: 6 mg/0.6 mL solution in a single-dose prefilled syringe for manual use only.
  • Injection: 6 mg/0.6 mL solution in a single-dose prefilled syringe co-packaged with the On-body Injector for Neulasta (Neulasta Onpro kit).

Storage And Handling

Neulasta Single-Dose Prefilled Syringe For Manual Use

Neulasta is supplied in a prefilled single-dose syringe for manual use containing 6 mg pegfilgrastim, supplied with a 27-gauge, ½-inch needle with an UltraSafe® Needle Guard.

The needle cap of the prefilled syringe contains dry natural rubber (a derivative of latex).

Neulasta is provided in a dispensing pack containing one sterile 6 mg/0.6 mL prefilled syringe (NDC 55513-190-01).

Neulasta prefilled syringe does not bear graduation marks and is intended only to deliver the entire contents of the syringe (6 mg/0.6 mL) for direct administration. Use of the prefilled syringe is not recommended for direct administration for pediatric patients weighing less than 45 kg who require doses that are less than the full contents of the syringe.

Store refrigerated between 36° to 46°F (2° to 8°C) in the carton to protect from light. Do not shake. Discard syringes stored at room temperature for more than 48 hours. Avoid freezing; if frozen, thaw in the refrigerator before administration. Discard syringe if frozen more than once.

Neulasta Onpro™ kit

Neulasta Onpro kit is provided in a carton containing one sterile prefilled syringe and one sterile On-body Injector for Neulasta (NDC 55513-192-01).

The single-dose prefilled syringe contains 0.64 mL of solution that delivers 6 mg/0.6 mL of pegfilgrastim when used with the On-body Injector for Neulasta. The prefilled syringe is supplied with a 27-gauge, ½-inch needle with an UltraSafe® Needle Guard. The syringe does not bear graduation marks and is only to be used with the On-body Injector for Neulasta.

The needle cap of the prefilled syringe contains dry natural rubber (a derivative of latex).

Store Neulasta Onpro kit in the refrigerator at 36°F to 46°F (2°C to 8°C) until ready for use. Because the On-body Injector for Neulasta is at room temperature during the period of use, Neulasta Onpro kit should not be held at room temperature longer than 12 hours prior to use. Discard Neulasta Onpro kit if stored at room temperature for more than 12 hours.

Do not use the On-body Injector for Neulasta if its packaging has been previously opened.

Manufactured by: Amgen Inc. One Amgen Center Drive Thousand Oaks, California 91320-1799. Revised: Apr 2016

Side Effects & Drug Interactions

SIDE EFFECTS

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

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 compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Neulasta clinical trials safety data are based upon 932 patients receiving Neulasta in seven randomized clinical trials. The population was 21 to 88 years of age and 92% female. The ethnicity was 75% Caucasian, 18% Hispanic, 5% Black, and 1% Asian. Patients with breast (n = 823), lung and thoracic tumors (n = 53) and 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.

The following adverse reaction data in Table 2 are from a randomized, double-blind, placebo-controlled study in patients with metastatic or non-metastatic breast cancer receiving docetaxel 100 mg/m²every 21 days (Study 3). A total of 928 patients were randomized to receive either 6 mg Neulasta (n = 467) or placebo (n = 461). The patients were 21 to 88 years of age and 99% female. The ethnicity was 66% Caucasian, 31% Hispanic, 2% Black, and < 1% Asian, Native American or other.

The most common adverse reactions occurring in ≥ 5% of patients and with a between-group difference of ≥ 5% higher in the pegfilgrastim arm in placebo controlled clinical trials are bone pain and pain in extremity.

Table 2: Adverse Reactions with ≥ 5% Higher Incidence in Neulasta Patients Compared to Placebo in (Study 3)

System Organ Class
Preferred Term
Placebo
(N= 461)

Neulasta 6 mg SC on Day 2
(N= 467)

Musculoskeletal and connective tissue disorders
Bone pain 26% 31%
Pain in extremity 4% 9%

Leukocytosis

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. No complications attributable to leukocytosis were reported in clinical studies.

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 assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Neulasta with the incidence of antibodies to other products may be misleading.

Postmarketing Experience

The following adverse reactions have been identified during post approval use 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.

DRUG INTERACTIONS

No formal drug interaction studies between Neulasta and other drugs have been performed. Increased hematopoietic activity of the bone marrow in response to growth factor therapy may result in transiently positive bone-imaging changes. Consider these findings when interpreting bone-imaging results.

Warnings & Precautions

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Splenic Rupture

Splenic rupture, including fatal cases, can occur following the administration of Neulasta. Evaluate for an enlarged spleen or splenic rupture in patients who report left upper abdominal or shoulder pain after receiving Neulasta.

Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) can occur in patients receiving Neulasta. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving Neulasta, for ARDS. Discontinue Neulasta in patients with ARDS.

Serious Allergic Reactions

Serious allergic reactions, including anaphylaxis, can occur in patients receiving Neulasta. The majority of reported events occurred upon initial exposure. Allergic reactions, including anaphylaxis, can recur within days after the discontinuation of initial anti-allergic treatment. Permanently discontinue Neulasta in patients with serious allergic reactions. Do not administer Neulasta to patients with a history of serious allergic reactions to pegfilgrastim or filgrastim.

Allergies To Acrylics

The On-body Injector for Neulasta uses acrylic adhesive. For patients who have reactions to acrylic adhesives, use of this product may result in a significant reaction.

Use In Patients With Sickle Cell Disorders

Severe sickle cell crises can occur in patients with sickle cell disorders receiving Neulasta. Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving filgrastim, the parent compound of pegfilgrastim.

Glomerulonephritis

Glomerulonephritis has occurred in patients receiving Neulasta. The diagnoses were based upon azotemia, hematuria (microscopic and macroscopic), proteinuria, and renal biopsy. Generally, events of glomerulonephritis resolved after dose reduction or discontinuation of Neulasta. If glomerulonephritis is suspected, evaluate for cause. If causality is likely, consider dose-reduction or interruption of Neulasta.

Leukocytosis

White blood cell (WBC) counts of 100 x 109/L or greater have been observed in patients receiving pegfilgrastim. Monitoring of complete blood count (CBC) during pegfilgrastim therapy is recommended.

Capillary Leak Syndrome

Capillary leak syndrome has been reported after G-CSF administration, including Neulasta, and is characterized by hypotension, hypoalbuminemia, edema and hemoconcentration. Episodes vary in frequency, severity 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.

Potential For Tumor Growth Stimulatory Effects On Malignant Cells

The granulocyte-colony stimulating factor (G-CSF) receptor through which pegfilgrastim and filgrastim act has been found on tumor cell lines. The possibility that pegfilgrastim acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which pegfilgrastim is not approved, cannot be excluded.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION).

Advise patients of the following risks and potential risks with Neulasta:

Advise patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Subsyndrome of Acute Radiation Syndrome) that efficacy studies of Neulasta for this indication could not be conducted in humans for ethical and feasibility reasons and that, therefore, approval of this use was based on efficacy studies conducted in animals [see Clinical Studies].

Instruct patients who self-administer Neulasta using the single-dose prefilled syringe of the:

  • Importance of following the Instructions for Use.
  • Dangers of reusing syringes.
  • Importance of following local requirements for proper disposal of used syringes.

Advise patients on the use of the On-body Injector for Neulasta:

  • Review the Patient Information and Patient Instructions for Use with the patient and provide the instructions to the patient.
  • Refer the patient to the dose delivery information written on the Patient Instructions for Use.
  • Tell the patient when their dose delivery of Neulasta will begin and when their dose delivery should be completed.
  • Advise the patient that serious allergic reactions can happen with Neulasta. Patients should have a caregiver nearby for the first use. Patients should plan to be in a place where they can appropriately monitor the On-body Injector for Neulasta during the approximately 45 minute Neulasta delivery and for an hour after the delivery. Advise the patient to avoid traveling, driving, or operating heavy machinery during hours 26-29 following application of the On-body Injector for Neulasta.
  • If the On-body Injector for Neulasta is placed on the back of the arm, remind the patient that a caregiver must be available to monitor the On-body Injector for Neulasta.
  • If a patient calls the healthcare provider regarding any On-body Injector for Neulasta problems, the healthcare provider is advised to call Amgen at 1-800-772-6436.
  • Advise the patient:
    • to call their healthcare provider immediately if the status light on the On-body Injector for Neulasta is flashing red (see the Patient Instructions for Use).
    • to inform their healthcare provider if the adhesive on the On-body Injector for Neulasta becomes saturated with fluid, or there is dripping, as this may be evidence of significant product leakage, resulting in inadequate or missed dose (see the Patient Instructions for Use).
    • to keep the On-body Injector for Neulasta dry for approximately the last 3 hours prior to the dose delivery start to better enable potential leak detection.
    • that the On-body Injector for Neulasta should only be exposed to temperatures between 41°F and 104°F (5°C-40°C)
    • to keep the On-body Injector for Neulasta at least 4 inches away from electrical equipment such as cell phones, cordless telephones, microwaves and other common appliances. Failure to keep the On-body Injector for Neulasta at least this recommended distance may interfere with operation and can lead to a missed or incomplete dose of Neulasta.
    • that if the needle is exposed after On-body Injector for Neulasta removal, place the used On-body Injector for Neulasta in a sharps disposal container to avoid accidental needle stick and call their healthcare provider immediately.
    • to remove the On-body Injector for Neulasta after the green light shines continuously and to place the used On-body Injector for Neulasta in a sharps disposal container (see the Patient Instructions for Use).
  • Advise the patient:
    • do not reapply the On-body Injector for Neulasta if the On-body Injector for Neulasta comes off before full dose is delivered and instead call their healthcare provider immediately.
    • avoid bumping the On-body Injector for Neulasta or knocking the On-body Injector for Neulasta off the body.
    • do not expose the On-body Injector for Neulasta to medical imaging studies, e.g. X-ray scan, MRI, CT scan, ultrasound and oxygen rich environments such as hyperbaric chambers to avoid On-body Injector for Neulasta damage and patient injury.
  • Advise the patient to avoid:
    • airport X-ray scans and request a manual pat down instead; remind patients who elect to request a manual pat down to exercise care to avoid having the On-body Injector for Neulasta dislodged during the pat down process.
    • sleeping on the On-body Injector for Neulasta or applying pressure on the On-body Injector for Neulasta as this may affect On-body Injector for Neulasta performance.
    • getting body lotions, creams, oils and cleaning agents near the On-body Injector for Neulasta as these products may loosen the adhesive.
    • using hot tubs, whirlpools, or saunas and avoid exposing the On-body Injector for Neulasta to direct sunlight as these may affect the drug.
    • peeling off or disturbing the On-body Injector for Neulasta adhesive before delivery of full dose is complete.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

No carcinogenicity or mutagenesis studies have been performed with pegfilgrastim.

Pegfilgrastim did not affect reproductive performance or fertility in male or female rats at cumulative weekly doses approximately 6 to 9 times higher than the recommended human dose (based on body surface area).

Reproductive And Developmental Toxicology

Pregnant rabbits were dosed with pegfilgrastim subcutaneously every other day during the period of organogenesis. At cumulative doses ranging from the approximate human dose to approximately 4 times the recommended human dose (based on body surface area), treated rabbits exhibited decreased maternal food consumption, maternal weight loss, as well as reduced fetal body weights and delayed ossification of the fetal skull; however, no structural anomalies were observed in the offspring from either study. Increased incidences of post-implantation losses and spontaneous abortions (more than half the pregnancies) were observed at cumulative doses approximately 4 times the recommended human dose, which were not seen when pregnant rabbits were exposed to the recommended human dose.

Three studies were conducted in pregnant rats dosed with pegfilgrastim at cumulative doses up to approximately 10 times the recommended human dose at the following stages of gestation: during the period of organogenesis, from mating through the first half of pregnancy, and from the first trimester through delivery and lactation. No evidence of fetal loss or structural malformations was observed in any study. Cumulative doses equivalent to approximately 3 and 10 times the recommended human dose resulted in transient evidence of wavy ribs in fetuses of treated mothers (detected at the end of gestation but no longer present in pups evaluated at the end of lactation).

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. Pegfilgrastim was embryotoxic and increased pregnancy loss in pregnant rabbits that received cumulative doses approximately 4 times the recommended human dose (based on body surface area). Signs of maternal toxicity occurred at these doses. Neulasta should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.

In animal reproduction studies, when pregnant rabbits received pegfilgrastim at cumulative doses approximately 4 times the recommended human dose (based on body surface area), increased embryolethality and spontaneous abortions occurred. Signs of maternal toxicity (reductions in body weight gain/food consumption) and decreased fetal weights occurred at maternal doses approximately equivalent to the recommended human dose (based on body surface area). There were no structural anomalies observed in rabbit offspring at any dose tested. No evidence of reproductive/developmental toxicity occurred in the offspring of pregnant rats that received cumulative doses of pegfilgrastim approximately 10 times the recommended human dose (based on body surface area) [see Nonclinical Toxicology].

Nursing Mothers

It is not known whether pegfilgrastim is secreted in human milk. Other recombinant G-CSF products are poorly secreted in breast milk and G-CSF is not orally absorbed by neonates. Caution should be exercised when administered to a nursing woman.

Pediatric Use

The safety and effectiveness of Neulasta have been established in pediatric patients. No overall differences in safety were identified between adult and pediatric patients based on postmarketing surveillance and review of the scientific literature.

Use of Neulasta in pediatric patients for chemotherapy-induced neutropenia is based on adequate and well controlled studies in adults with additional pharmacokinetic and safety data in pediatric patients with sarcoma [see CLINICAL PHARMACOLOGY and Clinical Studies].

The use of Neulasta to increase survival in pediatric patients acutely exposed to myelosuppressive doses of radiation is based on efficacy studies conducted in animals and clinical data supporting the use of Neulasta in patients with cancer receiving myelosuppressive chemotherapy. Efficacy studies of Neulasta could not be conducted in humans with acute radiation syndrome for ethical and feasibility reasons. Results from population modeling and simulation indicate that two doses of Neulasta (Table 1), administered one week apart provide pediatric patients with exposures comparable to that in adults receiving two 6 mg doses one week apart [see DOSAGE AND ADMINISTRATION, CLINICAL PHARMACOLOGY and Clinical Studies].

Geriatric Use

Of the 932 patients with cancer who received Neulasta in clinical studies, 139 (15%) were aged 65 and over, and 18 (2%) were aged 75 and over. No overall differences in safety or effectiveness were observed between patients aged 65 and older and younger patients.

Renal Impairment

Renal dysfunction had no effect on the pharmacokinetics of pegfilgrastim. Therefore, pegfilgrastim dose adjustment in patients with renal dysfunction is not necessary [see CLINICAL PHARMACOLOGY].

Overdosage & Contraindications

OVERDOSE

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 absolute neutrophil count (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. The effectiveness of leukapheresis in the management of symptomatic individuals with Neulasta-induced leukocytosis has not been studied.

CONTRAINDICATIONS

Do not administer Neulasta to patients with a history of serious allergic reactions to pegfilgrastim or filgrastim.

Clinical Pharmacology

CLINICAL PHARMACOLOGY

Mechanism Of Action

Pegfilgrastim is a colony-stimulating factor that acts on hematopoietic cells by binding to specific cell surface receptors, thereby stimulating proliferation, differentiation, commitment, and end cell functional activation.

Pharmacodynamics

Animal data and clinical data in humans suggest a correlation between pegfilgrastim exposure and the duration of severe neutropenia as a predictor of efficacy. Selection of the dosing regimen of Neulasta is based on reducing the duration of severe neutropenia.

Pharmacokinetics

The pharmacokinetics of pegfilgrastim was studied in 379 patients with cancer. The pharmacokinetics of pegfilgrastim was nonlinear and clearance decreased with increases in dose. Neutrophil receptor binding is an important component of the clearance of pegfilgrastim, and serum clearance is directly related to the number of neutrophils. In addition to numbers of neutrophils, body weight appeared to be a factor. Patients with higher body weights experienced higher systemic exposure to pegfilgrastim after receiving a dose normalized for body weight. A large variability in the pharmacokinetics of pegfilgrastim was observed. The half-life of Neulasta ranged from 15 to 80 hours after subcutaneous injection. In healthy volunteers, the pharmacokinetics of pegfilgrastim were comparable when delivered subcutaneously via a manual prefilled syringe versus via the On-body Injector for Neulasta.

Specific Populations

No gender-related differences were observed in the pharmacokinetics of pegfilgrastim, and no differences were observed in the pharmacokinetics of geriatric patients ( ≥ 65 years of age) compared with younger patients ( < 65 years of age) [see Use in Specific Populations].

Renal Impairment

In a study of 30 subjects with varying degrees of renal dysfunction, including end stage renal disease, renal dysfunction had no effect on the pharmacokinetics of pegfilgrastim [see Use In Specific Populations].

Pediatric Patients With Cancer Receiving Myelosuppressive Chemotherapy

The pharmacokinetics and safety of pegfilgrastim were studied in 37 pediatric patients with sarcoma in Study 4 [see Clinical Studies]. The mean (± standard deviation [SD]) systemic exposure (AUC 0-inf ) of Neulasta after subcutaneous administration at 100 mcg/kg was 47.9 (± 22.5) mcg·hr/mL in the youngest age group (0 to 5 years, n = 11), 22.0 (± 13.1) mcg·hr/mL in the (6 to 11 years age group (n = 10), and 29.3 (± 23.2) mcg·hr/mL in the 12 to 21 years age group (n = 13). The terminal elimination half-lives of the corresponding age groups were 30.1 (± 38.2) hours, 20.2 (± 11.3) hours, and 21.2 (± 16.0) hours, respectively.

Patients Acutely Exposed To Myelosuppressive Doses Of Radiation

The pharmacokinetics of pegfilgrastim is not available in patients acutely exposed to myelosuppressive doses of radiation. Based on limited pharmacokinetic data in irradiated non-human primates, the area under the concentration-time curve (AUC), reflecting the exposure to pegfilgrastim in non-human primates following a 300 mcg/kg dose of Neulasta, appears to be greater than in humans receiving a 6 mg dose. Results from population modeling and simulation indicate that two 6 mg doses of Neulasta administered one week apart in adults result in clinically relevant effects on duration of grade 3 and 4 neutropenia. In addition, weight based dosing in pediatric patients weighing less than 45 kg [see DOSING AND ADMINISTRATION, Table 1] provides exposures comparable to those in adults receiving two 6 mg doses one week apart.

Clinical Studies

Patients With Cancer Receiving Myelosuppressive Chemotherapy

Neulasta was evaluated in three randomized, double-blind, controlled studies. Studies 1 and 2 were active-controlled studies that employed doxorubicin 60 mg/m²and docetaxel 75 mg/m²administered 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 (ANC < 0.5 x 109/L) with a mean duration of 5 to 7 days and a 30% to 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 major efficacy outcome measure of demonstrating that the mean days of severe neutropenia of Neulasta-treated patients did not exceed that of filgrastim-treated patients by more than 1 day in cycle 1 of chemotherapy. The mean days of cycle 1 severe neutropenia in Study 1 were 1.8 days in the Neulasta arm compared to 1.6 days in the filgrastim arm [difference in means 0.2 (95% CI -0.2, 0.6)] and in Study 2 were 1.7 days in the Neulasta arm compared to 1.6 days in the filgrastim arm [difference in means 0.1 (95% CI -0.2, 0.4)].

A secondary endpoint in both studies was days of severe neutropenia in cycles 2 through 4 with results similar to those for cycle 1.

Study 3 was a randomized, double-blind, placebo-controlled study that employed docetaxel 100 mg/m²administered 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 major trial outcome measure 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%, respectively, p < 0.001). The incidence of hospitalizations (1% versus 14%) and IV anti-infective use (2% versus 10%) for the treatment of febrile neutropenia was also lower in the Neulasta-treated patients compared to the placebo-treated patients.

Study 4 was a multicenter, randomized, open-label study to evaluate the efficacy, safety, and pharmacokinetics [see CLINICAL PHARMACOLOGY] of Neulasta in pediatric and young adult patients with sarcoma. Patients with sarcoma receiving chemotherapy age 0 to 21 years were eligible. Patients were randomized to receive subcutaneous Neulasta as a single dose of 100 mcg/kg (n= 37) or subcutaneous filgrastim at a dose 5 mcg/kg/day (n=6) following myelosuppressive chemotherapy. Recovery of neutrophil counts was similar in the Neulasta and filgrastim groups. The most common adverse reaction reported was bone pain.

Patients With Hematopoietic Subsyndrome Of Acute Radiation Syndrome

Efficacy studies of Neulasta could not be conducted in humans with acute radiation syndrome for ethical and feasibility reasons. Approval of this indication was based on efficacy studies conducted in animals and data supporting Neulasta's effect on severe neutropenia in patients with cancer receiving myelosuppressive chemotherapy [see DOSAGE AND ADMINISTRATION].

The recommended dose of Neulasta is two doses, 6 mg each, administered one week apart for humans exposed to myelosuppressive doses of radiation. For pediatric patients weighing less than 45 kg, dosing of Neulasta is weight based and is provided in Table 1 [see DOSAGE AND ADMINISTRATION]. This dosing regimen is based on population modeling and simulation analyses. The exposure associated with this dosing regimen is expected to provide sufficient pharmacodynamic activity to treat humans exposed to myelosuppressive doses of radiation [see CLINICAL PHARMACOLOGY]. The safety of Neulasta at a dose of 6 mg has been assessed on the basis of clinical experience in patients with cancer receiving myelosuppressive chemotherapy.

The efficacy of Neulasta for the acute radiation syndrome setting was studied in a randomized, placebo-controlled non-human primate model of radiation injury. Rhesus macaques were randomized to either a control (n=23) or treated (n=23) cohort. On study day 0, animals (n = 6 to 8 per irradiation day) were exposed to total body irradiation (TBI) of 7.50 ± 0.15 Gy delivered at 0.8 ± 0.03 Gy/min, representing a dose that would be lethal in 50% of animals by 60 days of follow-up (LD50/60). Animals were administered subcutaneous injections of a blinded treatment (control article [5% dextrose in water] or pegfilgrastim [300-319 mcg/kg/day]) on study day 1 and on study day 8. The primary endpoint was survival. Animals received medical management consisting of intravenous fluids, antibiotics, blood transfusions, and other support as required.

Pegfilgrastim significantly (at 0.0014 level of significance) increased 60-day survival in irradiated non-human primates: 91% survival (21/23) in the pegfilgrastim group compared to 48% survival (11/23) in the control group.

Medication Guide

PATIENT INFORMATION

Neulasta®
(nu-las-tah)
(pegfilgrastim) Injection

What is Neulasta?

Neulasta is a man-made form of granulocyte colony-stimulating factor (G-CSF). G-CSF is a substance produced by the body. It stimulates the growth of neutrophils, a type of white blood cell important in the body's fight against infection. Acute Radiation Syndrome: The effectiveness of Neulasta for this use was only studied in animals, because it could not be studied in people.

Do not take Neulasta if you have had a serious allergic reaction to human G-CSFs such as pegfilgrastim or filgrastim products.

Before you receive Neulasta, tell your healthcare provider about all of your medical conditions, including if you:

  • have a sickle cell disorder.
  • have kidney problems.
  • are allergic to latex. The needle cap on the prefilled syringe contains dry natural rubber (derived from latex). You should not give Neulasta using the prefilled syringe if you have latex allergies.
  • are pregnant or plan to become pregnant. It is not known if Neulasta will harm your unborn baby.
  • are breastfeeding or plan to breastfeed. It is not known if Neulasta passes into your breast milk.

Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How will I receive Neulasta?

  • Neulasta is given as an injection under your skin (subcutaneous injection) by a healthcare provider. If your healthcare provider decides that the subcutaneous injections can be given at home by you or your caregiver, follow the detailed “Instructions for Use” that comes with your Neulasta for information on how to prepare and inject a dose of Neulasta.
  • You and your caregiver will be shown how to prepare and inject Neulasta before you use it.
  • You should not inject a dose of Neulasta to children weighing less than 45kg from a Neulasta prefilled syringe. A dose less than 0.6 mL (6mg) cannot be accurately measured using the Neulasta prefilled syringe.
  • If you are receiving Neulasta because you are also receiving chemotherapy, the last dose of Neulasta should be injected at least 14 days before and 24 hour after your dose of chemotherapy.
  • If you miss a dose of Neulasta, talk to your healthcare provider about when you should give your next dose.

What are possible side effects of Neulasta?

Neulasta may cause serious side effects, including:

  • Spleen rupture. Your spleen may become enlarged and can rupture. A ruptured spleen can cause death. Call your healthcare provider right away if you have pain in the left upper stomach area or your left shoulder.
  • A serious lung problem called Acute Respiratory Distress Syndrome (ARDS). Call your healthcare provider or get emergency care right away if you have shortness of breath with or without a fever, trouble breathing, or a fast rate of breathing.
  • Serious allergic reactions. Neulasta can cause serious allergic reactions. These reactions can cause a rash over your whole body, shortness of breath, wheezing, dizziness, swelling around your mouth or eyes, fast heart rate, and sweating. If you have any of these symptoms, stop using Neulasta and call your healthcare provider or get emergency medical help right away.
  • Sickle cell crises. You may have a serious sickle cell crisis if you have a sickle cell disorder and receive Neulasta. Serious sickle cell crises have happened in people with sickle cell disorders receiving Neulasta that has sometimes led to death. Call your healthcare provider right away if you have symptoms of sickle cell crisis such as pain or difficulty breathing.
  • Kidney injury (glomerulonephritis). Neulasta can cause kidney injury. Call your healthcare provider right away if you develop any of the following symptoms:
    • swelling of your face or ankles
    • blood in your urine or dark colored urine
    • you urinate less than usual
  • Increased white blood cell count (leukocytosis). Your healthcare provider will check your blood during treatment with Neulasta.
  • Capillary Leak Syndrome. Neulasta can cause fluid to leak from blood vessels into your body's tissues. This condition is called “Capillary Leak Syndrome” (CLS). CLS can quickly cause you to have symptoms that may become life-threatening. Get emergency medical help right away if you develop any of the following symptoms:
    • swelling or puffiness and are urinating less than usual
    • trouble breathing
    • swelling of your stomach-area (abdomen) and feeling of fullness
    • dizziness or feeling faint
    • a general feeling of tiredness

The most common side effects of Neulasta are pain in the bones, arms, and legs.

These are not all the possible side effects of Neulasta.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Neulasta?

  • Store Neulasta in the refrigerator between 36°F to 46°F (2°C to 8°C).
  • Do not freeze.
  • Keep the prefilled syringe in the original carton to protect from light or physical damage.
  • Do not shake the prefilled syringe.
  • Take Neulasta out of the refrigerator 30 minutes before use and allow it to reach room temperature before preparing an injection.
  • Throw away (dispose of) any Neulasta that has been left at room temperature, 68°F to 77°F (20°C to 25°C), for more than 48 hours.

Keep the Neulasta prefilled syringe out of the reach of children.

General information about the safe and effective use of Neulasta.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Neulasta for a condition for which it was not prescribed. Do not give Neulasta to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Neulasta that is written for health professionals.

What are the ingredients in Neulasta?

Active ingredient: pegfilgrastim

Inactive ingredients: acetate, polysorbate 20, sodium, and sorbitol in water for injection.

Instructions for Use

Neulasta
(nu-las-tah)
(pegfilgrastim) Injection, for subcutaneous use

Single-Dose Prefilled Syringe

Guide to parts

Guide to parts - Illustration

Important: The needle is covered by the gray needle cap before use.

Important

Read the Patient Information for important information you need to know about Neulasta before using these Instructions for Use.

Before you use a Neulasta prefilled syringe, read this important information.

Storing the prefilled syringe

  • Store Neulasta in the refrigerator between 36°F to 46°F (2°C to 8°C).
  • Do not freeze.
  • Keep the prefilled syringe in the original carton to protect from light or physical damage.
  • Take the prefilled syringe out of the refrigerator 30 minutes before use and allow it to reach room temperature before preparing an injection.
  • Throw away (dispose of) any Neulasta that has been left at room temperature, 68°F to 77°F (20°C to 25°C), for more than 48 hours.
  • Keep the Neulasta prefilled syringe out of the reach of children.

Using the prefilled syringe

  • It is important that you do not try to give the injection unless you or yourcaregiver has received training from your healthcare provider.
  • Make sure the name Neulasta appears on the carton and prefilled syringe label.
  • Check the carton and prefilled syringe label to make sure the dose strength is 6 mg.
  • You should not inject a dose of Neulasta to children weighing less than 45 kg from a Neulasta prefilled syringe. A dose less than 0.6 mL (6mg) cannot be accurately measured using the Neulasta prefilled syringe.
  • Do not use a prefilled syringe after the expiration date on the label.
  • Do not shake the prefilled syringe.
  • Do not remove the gray needle cap from the prefilled syringe until you are ready to inject.
  • Do not use the prefilled syringe if the carton is open or damaged.
  • Do not use a prefilled syringe if it has been dropped on a hard surface. The prefilled syringe may be broken even if you cannot see the break. Use a new prefilled syringe.
  • Do not slide the blue safety guard over the needle before you give the injection. This will “activate” or lock the blue safety guard. Use another prefilled syringe that has not been activated and is ready to use.
  • The gray needle cap on the prefilled syringe contains dry natural rubber (made from latex). Tell your healthcare provider if you are allergic to latex. You should not give Neulasta using the prefilled syringe if you have latex allergies.

Call your healthcare provider if you have any questions.

Step 1: Prepare

A Remove the prefilled syringe carton from the refrigerator.

Put the original carton with any unused prefilled syringes back in the refrigerator.

Remove the syringe tray from the carton. On a clean, well-lit surface, place the syringe tray at room temperature for 30 minutes before you give an injection.

  • Do not use the prefilled syringe if the carton is damaged.
  • Do not try to warm the prefilled syringe by using a heat credit such as hot water or microwave.
  • Do not leave the prefilled syringe in direct sunlight.
  • Do not shake the prefilled syringe.

Open the tray by peeling away the cover. Grab the blue safety guard to remove the prefilled syringe from the tray.

remove the prefilled syringe - Illustration

For safety reasons:

  • Do not grab the plunger rod.
  • Do not grab the gray needle cap.

B. Inspect the medicine and prefilled syringe.

Inspect the medicine and prefilled syringe - Illustration

Make sure the medicine in the prefilled syringe is clear and colorless.

  • Do not use the prefilled syringe if:
    • The medicine is cloudy or discolored or contains flakes or particles.
    • Any part appears cracked or broken.
    • The prefilled syringe has been dropped.
    • The gray needle cap is missing or not securely attached.
    • The expiration date printed on the label has passed.

In all cases, use a new prefilled syringe and call your healthcare provider.

C. Gather all materials needed for the injection.

Wash your hands thoroughly with soap and water. On a clean, well-lit work surface, place the:

  • Prefilled syringe
  • Alcohol wipe
  • Cotton ball or gauze pad
  • Adhesive bandage
  • Sharps disposal container

Materials needed for the injection - Illustration

Step 2: Get ready

D. Prepare and clean the injection site(s).

Injection sites - Illustration

You can use:

  • Thigh
  • Stomach area (abdomen), except for a 2-inch area right around the navel (belly button)
  • Upper outer area of the buttocks (only if someone else is giving you the injection)
  • Outer area of upper arm (only if someone else is giving you the injection)

Clean the injection site with an alcohol wipe. Let the skin dry.

  • Do not touch this area again before injecting.
  • If you want to use the same injection site, make sure it is not the same spot on the injection site you used for a previous injection.
  • Do not inject into areas where the skin is tender, bruised, red, or hard. Avoid injecting into areas with scars or stretch marks.

E. Hold the prefilled syringe by the syringe barrel. Carefully pull the gray needle cap straight off and away from the body.

NEULASTA® (pegfilgrastim) Figure 6 Illustration

  • Do not remove the gray needle cap from the prefilled syringe until you are ready to inject.
  • Do not twist or bend the gray needle cap.
  • Do not hold the prefilled syringe by the plunger rod.
  • Do not put the gray needle cap back onto the prefilled syringe.

Important: Throw the gray needle cap into the sharps disposal container.

Step 3: Subcutaneous (under the skin) injection

F. Pinch the injection site to create a firm surface

Pinch the injection site - Illustration

Important: Keep skin pinched while injecting.

G. Hold the pinch. Insert the needle into the skin at 45 to 90 degrees.

Insert the needle into the skin - Illustration

H. Using slow and constant pressure, push the plunger rod until it reaches the bottom.

When done, gently pull the syringe off of the skin.

Push the plunger rod - Illustration

Important: When you remove the syringe, if it looks like the medicine is still in the syringe barrel, this means you have not received a full dose. Call your healthcare provider right away.

Step 4: Finish

Caution - Illustration

For your safety, pull the blue safety guard until it clicks and covers the needle.

Pull the blue safety guard - Illustration

Once extended, the blue safety guard will lock into position and will not slide back over the needle.

Keep your hands away from the needle at all times.

J. Discard (throw away) the used prefilled syringe

Discard (throw away) the used prefilled syringe - Illustration

  • Put the used prefilled syringe in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) the syringe in the household trash.
  • If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:
    • made of a heavy-duty plastic,
    • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
    • upright and stable during use,
    • leak-resistant, and
    • properly labeled to warn of hazardous waste inside the container.
  • When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal
  • Do not reuse the prefilled syringe.
  • Do not recycle the prefilled syringe or sharps disposal container or throw them into household trash.

Important: Always keep the sharps disposal container out of the reach of children.

K. Examine the injection site.

If there is blood, press a cotton ball or gauze pad on the injection site. Do not rub the injection site. Apply an adhesive bandage if needed.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Neulasta®
(pegfilgrastim)

Onpro™ kit
Healthcare Provider Instructions for Use

Guide to Parts

Neulasta Prefilled Syringe with Manual Needle Guard

Neulasta Prefilled Syringe with Manual Needle Guard - Illustration

On-body Injector for Neulasta

On-body Injector for Neulasta - Illustration

Important

READ THE FOLLOWING INSTRUCTIONS BEFORE USING THE ON-BODY INJECTOR

Warning: Do not use Neulasta Onpro kit to deliver any other drug product.

  • See Prescribing Information for information on Neulasta.
  • The On-body Injector is for adult patients only.
  • The On-body Injector is not recommended for patients with Hematopoietic Subsyndrome of Acute Radiation Syndrome.
  • Store Neulasta Onpro kit in the refrigerator at 36°F to 46°F (2°C to 8°C) until ready for use. If Neulasta Onpro kit is stored at room temperature for more than 12 hours, do not use. Start again with a new Neulasta Onpro kit.
  • Keep the prefilled syringe in the Neulasta Onpro kit carton until use to protect from light.
  • For patients who have had severe skin reactions to acrylic adhesives, consider the benefit:risk profile before administering pegfilgrastim via the On-body Injector for Neulasta.
  • The On-body Injector should be applied to intact, non-irritated skin on the abdomen or back of the arm. The back of the arm may only be used if there is a caregiver available to monitor the status of the On-body Injector.
  • DO NOT:
    • freeze Neulasta Onpro kit.
    • shake the prefilled syringe.
    • separate the components of Neulasta Onpro kit until ready for use.
    • modify the On-body Injector.
    • warm Neulasta Onpro kit components using a heat credit.
    • use Neulasta Onpro kit if expiry date on the carton or any of the Neulasta Onpro kit components has passed.
    • use if the name Neulasta does not appear on the Neulasta Onpro kit carton.
    • attempt to reapply On-body Injector.
    • use if either the On-body Injector or prefilled syringe is dropped. Start again with a new Neulasta Onpro kit.

For all questions, call Amgen at 1-800-772-6436. If a patient calls you regarding any On-body Injector problems, call Amgen at 1-800-772-6436.

Step 1: Prepare

A Remove Neulasta Onpro kit from refrigerator. Check to make sure it contains:

  • One Neulasta prefilled syringe
  • One On-body Injector for Neulasta
  • Neulasta package insert
  • Instructions for use:
    • for healthcare provider
    • for patient
  • Reference guide

DO NOT use On-body Injector if its packaging has been previously opened.

Wash hands thoroughly. Prepare and clean On-body injector application site.

On-body injector application site - Illustration

Choose the flattest site for On-body Injector application. Consult with your patient regarding their ability to remove and monitor the entire On-body Injector.

You can use:

  • Left or right side of abdomen, except for a 2-inch area right around navel.
  • Back of upper arm, only if there is a caregiver available to monitor the status of the On-body Injector.

Choose an area larger than the adhesive pad, and clean it with an alcohol swab. Allow skin to completely dry.

DO NOT touch this area again before attaching On-body Injector.

You should avoid:

  • Areas with scar tissues, moles, or excessive hair. In case of excessive hair, carefully trim hair to get On-body Injector close to skin.
  • Areas where belts, waistbands, or tight clothing may rub against, disturb, or dislodge On-body Injector.
  • Surgical sites.
  • Areas where On-body Injector will be affected by folds in skin.

The following is an overview of On-body Injector preparation steps. Read this section first.

When ready, proceed to Step 2: Get Ready Section.

Caution - Illustration

Before you apply On-body Injector to your patient, locate medicine port on blue needle cover to fill the On-body Injector with Neulasta.

Please note: During filling, beeping will sound and the On-body Injector will be activated.

After activation, you will have 3 minutes to:

  1. Completely empty syringe contents into medicine port.
  2. Remove syringe from port and pull down needle safety guard over the exposed needle.
  3. Remove blue needle cover from back of On-body Injector.
  4. Peel away the two pieces of white adhesive backing from the back of the On-body Injector.
  5. Attach On-body Injector to back of patient's upper arm or abdomen.

On-body Injector will deploy cannula in 3 minutes, even if not applied to patient. If not on patient's body in 3 minutes, do not use the On-body Injector. Start again with a new Neulasta Onpro kit.

When you feel you are ready, please continue...

Step 2: Get Ready

A. Remove Neulasta prefilled syringe from tray.

Remove Neulasta prefilled syringe from tray -  Illustration

For safety reasons:

DO NOT grasp gray needle cap.

DO NOT put the gray needle cap back onto syringe.

DO NOT grasp clear plunger.

B. Inspect medicine and Neulasta prefilled syringe. The Neulasta liquid should always be clear and colorless.

Inspect medicine and Neulasta prefilled syringe - Illustration

DO NOT use Neulasta prefilled syringe if:

  • Liquid contains particulate matter or discoloration is observed prior to administration.
  • Any part appears cracked or broken.
  • The gray needle cap is missing or not securely attached.
  • The expiration date printed on the label has passed.

DO NOT remove gray needle cap until ready to fill On-body Injector.

DO NOT pull needle safety guard down over the needle until filling is complete.

  • In all the above cases, start again with a new Neulasta Onpro kit. Call Amgen at 1-800-772-6436.
  • The prefilled syringe gray needle cap contains dry natural rubber, which is derived from latex.

C. Carefully remove gray needle cap straight outfrom the syringe and away from your body. Check syringe, and remove air bubbles.

Carefully remove gray needle cap - Illustration

  • Take care to expel air only and not medicine.

A small droplet at the tip of the needle during air purging is normal.

DO NOT recap syringe.

D. Using blue needle cover, to avoid bending the needle and spilling medicine, insert syringe needle at 90 degrees all the way into medicine port. Slowly empty the entire syringe contents. Remove empty syringe from the medicine port.

When beeping sounds and the status light flashes amber, the 3-minute countdown begins.

Insert syringe needle at 90 degrees all the way into medicine port - Illustration

DO NOT insert needle into medicine port at other than a 90 degree angle

DO NOT insert needle more than once.

DO NOT remove blue needle cover before filling the On-body Injector.

E. Pull needle safety guard down until it clicks and covers needle. Dispose of empty syringe in a sharps container.

Pull needle safety guard down - Illustration

F. Check to see if the On-body Injector is full.

Check to see if the On-body Injector is full - Illustration

You should see:

  • amber status light flashing.
  • black line next to FULL on the fill indicator

If this is not the case, do not use. Start again with a new Neulasta Onpro kit, and call Amgen at 1-800-772-6436.

Step 3: Apply

A. Firmly lift and remove blue needle cover away from On-body Injector.

Firmly lift and remove blue needle cover away from On-body Injector - Illustration

A drop of medicine may be visible on needle tip when blue needle cover is removed.

B. To expose the adhesive pad, use both pull tabs, one at a time, to peel the two pieces of white adhesive backing away from On-body Injector.

Peel the two pieces of white adhesive backing away - Illustration

DO NOT touch or contaminate automatic needle area.

DO NOT pull off adhesive pad or fold it.

DO NOT use if the needle or cannula is extended past the adhesive or is extended before the On-body Injector is placed on patient.

In all cases, start again with a new Neulasta Onpro kit. Call Amgen at 1-800-772-6436.

C. Apply On-body Injector securely to patient with entire On-body Injector visible so it can be monitored by patient or caregiver.Before cannula deploys, place On-body Injector on your selected site, and run your finger around entire adhesive pad to make sure it is securely attached.

Back of Upper Arm

Apply On-body Injector securely - Illustration

Abdomen

Apply On-body Injector securely - Illustration

STOP! Do not worry if On-body Injector is quiet. When 3 minutes are up, On-body Injector will beep.

Caution - Illustration

D. Beeping will tell you the cannula is about to insert. You may hear a series of clicks. This is okay.

A long beep will sound, and the status light will turn to green. This means the cannula insertion is complete.

Beeps and meaning - Illustration

  • If the adhesive folds over near the cannula window or there are folds anywhere that prevent the On-body Injector from securely adhering, remove the On-body Injector. Start again with a new Neulasta Onpro kit and call Amgen at 1-800-772-6436.

Step 4: Finish

A Fill in the Dose Delivery Information section in the patient instructions. Be sure to include when the On-body Injector was applied, when the dose will begin, and your contact information. Review this information with the patient.

Review each step in the patient instructions with your patient. Give your patient the instructions, and reference guide to take home. Before your patient goes home, make sure your patient understands:

  • The On-body Injector will always flash a slow green light to let them know it is working properly.
  • After approximately 27 hours, beeps will signal that the dose delivery will begin in 2 minutes.
  • When the dose delivery starts it will take about 45 minutes to complete. During this time, the On-body Injector will flash a fast green light.
  • The patient should remain in a place where they can monitor the On-body Injector for the entire dose delivery. The patient should avoid activities and settings that may interfere with monitoring during the dosing of Neulasta administered by the On-body Injector. For example, avoid traveling, driving, or operating heavy machinery during hours 26-29 following application of the On-body Injector (this includes the approximately 45-minute delivery period plus an hour post-delivery).
  • If the patient has an allergic reaction during the delivery of Neulasta, the patient should remove the On-body Injector and call his or her healthcare provider or seek emergency care right away.
  • If placed on the back of the arm, remind the patient that a caregiver must be available to monitor the On-body Injector.
  • When the dose delivery is complete, the patient or caregiver will hear a beep and see a solid green light.
  • Always dispose of the empty On-body Injector in a sharps disposal container as instructed by your healthcare provider or by state or local laws.
  • Keep the On-body Injector at least 4 inches away from electrical equipment such as cell phones, cordless telephones, microwaves and other common appliances. Failure to keep the On-body Injector at least this recommended distance may interfere with operation and can lead to a missed or incomplete dose of Neulasta.

Attention!

What to do if you hear beeping or when you look at status light and it is flashing red.

What to do if you hear beeping - Illustration

If at any time the On-body Injector beeps continuously for 5 minutes, and the status light is flashing red, take the On-body Injector off of the patient.

DO NOT apply On-body Injector to patient if red error light is on.

DO NOT leave On-body Injector on patient if red error light is on. In all cases, do not use. Start over with a new Neulasta Onpro kit, and call Amgen at 1-800772-6436.

What to do if the adhesive becomes saturated with fluid or the On-body Injector is dripping.

NEULASTA® (pegfilgrastim) Figure 30 Illustration

If patient reports an On-body Injector leak, they might not have received full dose. Schedule a follow-up appointment, and report the incident to Amgen at 1-800-772-6436.

Do not expose the On-body Injector for Neulasta to the following environments as the On-body Injector may be damaged and the patient could be injured:

Symbols & meanings -  Illustration

Electromagnetic Compatibility

The information contained in this section (such as separation distances) is, in general, specifically written in regard to the On-body Injector for Neulasta. The numbers provided will not guarantee faultless operation but should provide reasonable assurance of such. This information may not be applicable to other medical electrical equipment; older equipment may be particularly susceptible to interference.

General Notes:

Medical electrical equipment requires special precautions regarding electromagnetic compatibility (EMC), and needs to be installed and put into service according to the EMC information provided in this document.

Portable and mobile RF communications equipment can affect medical electrical equipment.

Cables and accessories not specified within the instructions for use are not authorized. Using cables and/or accessories may adversely impact safety, performance, and electromagnetic compatibility (increased emission and decreased immunity).

Care should be taken if the On-body Injector for Neulasta is used adjacent to other electrical equipment; if adjacent use is inevitable, the On-body Injector for Neulasta should be observed to verify normal operation in this setting.

Electromagnetic Emissions

The On-body Injector for Neulasta is intended for use in the electromagnetic environment specified below. The user of the On-body Injector for Neulasta should ensure that it is used in such an environment.

Emissions Compliance according to Electromagnetic environment
RF Emissions (CISPR 11) Group 1 The On-body Injector for Neulasta uses RF energy only for its internal function. Therefore, its RF emissions are very low and are not likely to cause any interference in nearby equipment.
CISPR B Emissions Classification Class B  

Electromagnetic Immunity

The On-body Injector for Neulasta is intended for use in the electromagnetic environment specified below. The user of this equipment should ensure that it is used in such an environment.

Immunity Test IEC 60601 Test Level Compliance Level Electromagnetic Environment -Guidance
ESD IEC 610000-4-2 ±6kV Contact ±8kV Air 6kV Contact ±8kV Air Floors should be wood, concrete or ceramic tile. If floors are synthetic, the r/h should be at least 30%.
Power Frequency 50/60 Hz Magnetic Field IEC 61000-4-8 3A/m 3A/m Power frequency magnetic fields should be that of typical commercial or hospital environment.
Radiated RF Fields 61000-4-3 3 V/m 80 MHz to 2.5 GHz (E1)=3V/m Portable and mobile communications equipment should be separated from the On-body Injector for Neulasta by no less than the distances calculated/listed below: D=(3.5/V1)(√P)150 kHz to 80 MHz D=(3.5/E1)(√P)80 to 800 MHz D=(7/E1)(√P)800 MHz to 2.5 GHz Where P is the max power in watts and D is the recommended separation distance in meters. Field strengths from fixed transmitters, as determined by an electromagnetic site survey, should be less than the compliance levels (V1 and E1). Interference may occur in the vicinity of equipment containing a transmitter.

Recommended separation distances between portable and mobile RF communications equipment and the On-body Injector for Neulasta

You can help prevent electromagnetic interference by maintaining a minimum distance between portable and mobile RF communications equipment (transmitters) and the On-body Injector for Neulasta, as recommended below, according to the maximum power of the communication equipment.

Rated maximum output power of transmitter, in watts Separation distance according to frequency of transmitter, in meters
150 kHz to 80 MHz D=(3.5/V1)( √P) 80 to 800 MHz D=(3.5/E1)( √P) 800 MHz to 2.5 GHz D=(7/E1)(√P)
0.01 0.11667 0.11667 0.23333
0.1 0.36894 0.36894 0.73785
1 1.1667 1.1667 2.3333
10 3.6894 3.6894 7.3785
100 11.667 11.667 23.333

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