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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 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.
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:
- Splenic rupture and splenomegaly
- Acute Respiratory Distress Syndrome
- Serious allergic reactions
- Sickle cell crisis
- Capillary Leak Syndrome
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.
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 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].
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.
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].
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 dysfunction had no effect on the pharmacokinetics of pegfilgrastim. Therefore, pegfilgrastim dose adjustment in patients with renal dysfunction is not necessary [see CLINICAL PHARMACOLOGY].This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 5/9/2016
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