UDENYCA

Colony-stimulating Factors

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Pegfilgrastim is available as a single-dose prefilled syringe for manual use, a Neulasta Onpro kit containing the On-body Injector with a single-dose prefilled syringe, and a single-dose prefilled autoinjector.
Do not use the single-use prefilled syringe intended for manual injection with the On-body Injector or the patient will receive less than the recommended dose; additionally, do not fill the On-body Injector with any other drug.
Do not use the single-use prefilled syringe contained in the Neulasta Onpro Kit as a manual injection or the patient will receive more than the recommended dose.
Do not administer pegfilgrastim between 14 days before and 24 hours after administration of cytotoxic chemotherapy.
Manual Use:
Read and become familiar with the manufacturer's "Instructions for Use" prior to preparing or injecting the prefilled syringe.
Store prefilled syringes in the refrigerator between 36 and 46 degrees Fahrenheit (2 to 8 degrees Celsius) in the carton to protect from light; do not shake.
Allow the prefilled syringe to reach room temperature (for a minimum of 30 minutes; or a minimum of 15 to 30 minutes for pegfilgrastim-bmez) before administering; discard syringes kept at room temperature longer than 48 hours for pegfilgrastim (originator product) and pegfilgrastim-cbqv; 72 hours for pegfilgrastim-jmdb, pegfilgrastim-pbbk and pegfilgrastim-fpgk; 120 hours for pegfilgrastim-bmez; or 15 days for pegfilgrastim-apgf.
Do not freeze the pegfilgrastim prefilled syringe.
If the pegfilgrastim prefilled syringe is frozen, allow the syringe to thaw in the refrigerator prior to injection; do not use the syringe if it has been frozen more than once.
Subcutaneous Injection Using Prefilled Syringe for Manual Use:
Do not activate the needle guard prior to injection; pull the needle cover straight off.
Do not directly administer doses less than 6 mg (0.6 mL) from the prefilled syringe due to the potential for dosing errors. The prefilled syringe does not have graduation marks necessary for the accurate measurement of doses.
Inject pegfilgrastim in a recommended injection site (i.e., the outer area of the upper arm, the abdomen excluding the 2-inch area around the navel, the front of the middle thigh, and the upper outer areas of the buttocks). [62397] [63242] [63726]
On-body Injector:
Read and become familiar with the manufacturer's "Instructions for Use" prior to preparing or applying the On-body Injector.
The On-body Injector is not recommended for use in patients acutely exposed to radiation; additionally, the On-body Injector has not been studied in pediatric patients.
Apply the On-Body Injector containing pegfilgrastim on the patient after chemotherapy completes.
Thoroughly clean the application site with alcohol to enhance On-Body Injector adherence to the skin; avoid the use of lotions, creams, or oils on arms or the abdomen before the next scheduled dose.
Once applied, the On-Body Injector containing pegfilgrastim should be kept at temperatures between 41 and 104 degrees F (5 to 40 degrees C).
The On-body Injector should remain dry starting at 24 hours after placement (approximately 3 hours before drug delivery begins).
Report problems with the On-body Injector to Amgen at 1-800-772-6436.
Preparation:
Locate the medicine port on the blue needle cover; insert the single-use, prefilled syringe (provided in the kit) needle at 90 degrees and slowly fill the On-Body Injector with pegfilgrastim.
The On-Body Injector needs to be filled and placed on the patient within 3 minutes after activation; a beeping sound and an amber light flashing signals activation.
Application:
Remove the blue needle cover from the On-Body Injector, pull both tabs (one at a time) to uncover the adhesive pad, and place the On-Body Injector on the patient.
Do not use other materials to hold the On-Body Injector in place that could cover audio/visual indicators or compress the on-body injector against the patient's skin; if additional adhesion is deemed appropriate, an adhesive extender that fits around the On-Body Injector can be obtained by calling 1-844-696-3852.
The recommended placement site is the abdomen (apply horizontally with light facing the navel) or back of the arm (apply vertically with light facing down toward the elbow).
Avoid placement on areas of the skin that have swelling, redness, cuts, wounds, or abrasions.
A long beeping sound and a green light indicates that the On-Body Injector cannula has been inserted.
Discard the kit and use a new one if the cannula deploys prior to On-Body Injector placement.
If the red error light is on, do not place or immediately remove the On-Body Injector.
If the patient reports that the adhesive became wet (i.e., pegfilgrastim leaked) or the On-Body Injector dripped, evaluate if the full dose was received.
Subcutaneous Injection Using On-body Injector:
The dose will be delivered over about 45 minutes at approximately 27 hours after placement.
The patient or a caregiver should monitor the site during the dose administration period and for 1 hour after delivery to ensure the full dose is received and to monitor for symptoms of an allergic reaction.
For a missed dose due to On-body Injector failure or leakage, a new dose using the single prefilled syringe for manual use should be administered as soon as possible.[62397]
Prefilled Autoinjector:
Do not use the prefilled autoinjector in pediatric patients weighing less than 45 kg; the autoinjector delivers the entire 6-mg dose and is not adjustable.
Read and become familiar with the manufacturer's "Instructions for Use" prior to preparing or injecting the autoinjector.
Store prefilled syringes in the refrigerator between 36 and 46 degrees Fahrenheit (2 to 8 degrees Celsius) in the carton to protect from light; do not shake.
Allow the prefilled syringe to reach room temperature (for a minimum of 30 minutes) before administering; discard syringes kept at room temperature longer than 48 hours.
Do not freeze the pegfilgrastim prefilled syringe.
If the pegfilgrastim prefilled syringe is frozen, allow the syringe to thaw in the refrigerator prior to injection; do not use the syringe if it has been frozen more than once.
Subcutaneous Injection Using Prefilled Autoinjector:
Do not remove the clear cap from the prefilled autoinjector until you are ready to inject.
Inject pegfilgrastim in a recommended injection site (i.e., the back of the upper arm, the abdomen excluding the 2-inch area around the navel, the front of the middle thigh, and the upper outer areas of the buttocks).

anaphylactoid reactions / Rapid / Incidence not known
acute respiratory distress syndrome (ARDS) / Early / Incidence not known
splenic rupture / Delayed / Incidence not known
sickle-cell crisis / Delayed / Incidence not known
vasculitis / Delayed / Incidence not known
glomerulonephritis / Delayed / Incidence not known
azotemia / Delayed / Incidence not known
capillary leak syndrome / Early / Incidence not known
aortitis / Delayed / Incidence not known
leukemia / Delayed / Incidence not known
new primary malignancy / Delayed / Incidence not known

bone pain / Delayed / 31.0-31.0
antibody formation / Delayed / 0-6.0
thrombocytopenia / Delayed / Incidence not known
contact dermatitis / Delayed / Incidence not known
erythema / Early / Incidence not known
splenomegaly / Delayed / Incidence not known
bleeding / Early / Incidence not known
proteinuria / Delayed / Incidence not known
hematuria / Delayed / Incidence not known
edema / Delayed / Incidence not known
hypotension / Rapid / Incidence not known
hypoalbuminemia / Delayed / Incidence not known

leukocytosis / Delayed / 0-1.0
rash / Early / Incidence not known
pruritus / Rapid / Incidence not known
flushing / Rapid / Incidence not known
urticaria / Rapid / Incidence not known
injection site reaction / Rapid / Incidence not known
back pain / Delayed / Incidence not known
fever / Early / Incidence not known
malaise / Early / Incidence not known
abdominal pain / Early / Incidence not known

Fulphila, Fylnetra, Neulasta, Nyvepria, Stimufend, UDENYCA, Ziextenzo

Rx

Granulocyte colony-stimulating growth factor
Indicated to decrease the incidence of infection in patients with non-myeloid malignancies receiving myelosuppressive chemotherapy associated with a clinically significant incidence of febrile neutropenia and to increase survival in patients acutely exposed to myelosuppressive doses of radiation
Acute respiratory distress syndrome, fatal splenic rupture, and glomerulonephritis have been reported

Note: Do not use the prefilled autoinjector in pediatric patients weighing less than 45 kg.

6 mg subcutaneously once per chemotherapy cycle, at least 24 hours after administration of cytotoxic chemotherapy. Pegfilgrastim should not be administered within 14 days prior to the next cycle of cytotoxic chemotherapy. [63726] [62397] [63242] Febrile neutropenia (defined as a body temperature of 38.2 degrees Celsius or higher and an absolute neutrophil count (ANC) less than 0.5 x 109 cells/L on the same day of the fever or the day after) occurred in significantly fewer breast cancer patients who received a single subcutaneous injection of pegfilgrastim 6 mg (n = 463) compared with placebo (n = 465) starting on day 2 of the first cycle of docetaxel 100 mg/m2 IV every 3 weeks (1% vs. 17%; p less than 0.001). Additionally, the incidence of febrile neutropenia-related hospitalization (1% vs. 14%; p less than 0.001) and IV anti-infective agent use (2% vs. 10%; p less than 0.001) was significantly lower with pegfilgrastim compared with placebo in this multicenter, double-blind, randomized trial.[58752] Treatment with a single subcutaneous dose of pegfilgrastim 6 mg followed by daily placebo injections (n = 75) was noninferior to subcutaneous filgrastim 5 mcg/kg/day (n = 77) in patients with breast cancer who received doxorubicin 60 mg/m2 and docetaxel 75 mg/m2 IV on day 1 repeated every 3 weeks in a multicenter, double-blind, randomized study. Treatment was begun starting on day 2 or approximately 24 hours after chemotherapy and continued until the ANC was 10 x 109 cells/L or greater. The mean duration of grade 4 neutropenia (defined as an absolute neutrophil count less than 0.5 x 109 cells/L) in cycle 1 (primary endpoint) was 1.8 days in the pegfilgrastim arm and 1.6 days in the filgrastim arm (mean difference = 0.23 days; 95% CI, -0.15 to 0.63 days); the noninferiority of pegfilgrastim was demonstrated when the upper limit of the mean difference 95% CI was less than 1 day. In a multicenter, randomized, open-label clinical trial of pediatric and young adult patients with sarcoma (age 21 or younger), the recovery of neutrophil counts following myelosuppressive chemotherapy was similar in patients treated with pegfilgrastim 100 mcg/kg (n = 37) or filgrastim 5 mcg/kg/day subcutaneously (n = 6).[46590]

4 mg subcutaneously once per chemotherapy cycle, at least 24 hours after administration of cytotoxic chemotherapy. Pegfilgrastim should not be administered within 14 days prior to the next cycle of cytotoxic chemotherapy. In a multicenter, randomized, open-label clinical trial of pediatric and young adult patients with sarcoma (age 21 or younger), the recovery of neutrophil counts following myelosuppressive chemotherapy was similar in patients treated with pegfilgrastim 100 mcg/kg (n = 37) or filgrastim 5 mcg/kg/day subcutaneously (n = 6). [63726] [62397] [63242]

2.5 mg subcutaneously once per chemotherapy cycle, at least 24 hours after administration of cytotoxic chemotherapy. Pegfilgrastim should not be administered within 14 days prior to the next cycle of cytotoxic chemotherapy. In a multicenter, randomized, open-label clinical trial of pediatric and young adult patients with sarcoma (age 21 or younger), the recovery of neutrophil counts following myelosuppressive chemotherapy was similar in patients treated with pegfilgrastim 100 mcg/kg (n = 37) or filgrastim 5 mcg/kg/day subcutaneously (n = 6).

1.5 mg subcutaneously once per chemotherapy cycle, at least 24 hours after administration of cytotoxic chemotherapy. Pegfilgrastim should not be administered within 14 days prior to the next cycle of cytotoxic chemotherapy. In a multicenter, randomized, open-label clinical trial of pediatric and young adult patients with sarcoma (age 21 or younger), the recovery of neutrophil counts following myelosuppressive chemotherapy was similar in patients treated with pegfilgrastim 100 mcg/kg (n = 37) or filgrastim 5 mcg/kg/day subcutaneously (n = 6).

0.1 mg/kg subcutaneously once per chemotherapy cycle, at least 24 hours after administration of cytotoxic chemotherapy. Pegfilgrastim should not be administered within 14 days prior to the next cycle of cytotoxic chemotherapy. In a multicenter, randomized, open-label clinical trial of pediatric and young adult patients with sarcoma (age 21 or younger), the recovery of neutrophil counts following myelosuppressive chemotherapy was similar in patients treated with pegfilgrastim 100 mcg/kg (n = 37) or filgrastim 5 mcg/kg/day subcutaneously (n = 6).

Note: Do not use the prefilled autoinjector in pediatric patients weighing less than 45 kg.

6 mg subcutaneously once, followed by a second dose of 6 mg subcutaneously 1 week later, for a total of two doses. Administer the first dose as soon as possible after suspected or confirmed exposure to radiation levels greater than 2 gray (Gy). Do not delay administration of pegfilgrastim 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. The use of pegfilgrastim to increase survival after acute radiation exposure is based on efficacy studies conducted in animals, in addition to data regarding the effect of pegfilgrastim on severe neutropenia in cancer patients receiving myelosuppressive chemotherapy; efficacy studies in humans for acute radiation syndrome were not conducted for ethical and feasibility reasons. In animal studies, pegfilgrastim significantly increased 60-day survival in irradiated non-human primates (91% vs. 48%; p = 0.0014).

4 mg subcutaneously once, followed by a second dose of 4 mg subcutaneously 1 week later, for a total of two doses. Administer the first dose as soon as possible after suspected or confirmed exposure to radiation levels greater than 2 gray (Gy). Do not delay administration of pegfilgrastim 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. The use of pegfilgrastim to increase survival after acute radiation exposure is based on efficacy studies conducted in animals, in addition to data regarding the effect of pegfilgrastim on severe neutropenia in cancer patients receiving myelosuppressive chemotherapy; efficacy studies in humans for acute radiation syndrome were not conducted for ethical and feasibility reasons. In animal studies, pegfilgrastim significantly increased 60-day survival in irradiated non-human primates (91% vs. 48%; p = 0.0014). Dosing in pediatric patients weighing less than 45 kg is based on population modeling and simulation analysis.

2.5 mg subcutaneously once, followed by a second dose of 2.5 mg subcutaneously 1 week later, for a total of two doses. Administer the first dose as soon as possible after suspected or confirmed exposure to radiation levels greater than 2 gray (Gy). Do not delay administration of pegfilgrastim 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. The use of pegfilgrastim to increase survival after acute radiation exposure is based on efficacy studies conducted in animals, in addition to data regarding the effect of pegfilgrastim on severe neutropenia in cancer patients receiving myelosuppressive chemotherapy; efficacy studies in humans for acute radiation syndrome were not conducted for ethical and feasibility reasons. In animal studies, pegfilgrastim significantly increased 60-day survival in irradiated non-human primates (91% vs. 48%; p = 0.0014). Dosing in pediatric patients weighing less than 45 kg is based on population modeling and simulation analysis.

1.5 mg subcutaneously once, followed by a second dose of 1.5 mg subcutaneously 1 week later, for a total of two doses. Administer the first dose as soon as possible after suspected or confirmed exposure to radiation levels greater than 2 gray (Gy). Do not delay administration of pegfilgrastim 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. The use of pegfilgrastim to increase survival after acute radiation exposure is based on efficacy studies conducted in animals, in addition to data regarding the effect of pegfilgrastim on severe neutropenia in cancer patients receiving myelosuppressive chemotherapy; efficacy studies in humans for acute radiation syndrome were not conducted for ethical and feasibility reasons. In animal studies, pegfilgrastim significantly increased 60-day survival in irradiated non-human primates (91% vs. 48%; p = 0.0014). Dosing in pediatric patients weighing less than 45 kg is based on population modeling and simulation analysis.

0.1 mg/kg subcutaneously once, followed by a second dose of 0.1 mg/kg subcutaneously 1 week later, for a total of two doses. Administer the first dose as soon as possible after suspected or confirmed exposure to radiation levels greater than 2 gray (Gy). Do not delay administration of pegfilgrastim 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. The use of pegfilgrastim to increase survival after acute radiation exposure is based on efficacy studies conducted in animals, in addition to data regarding the effect of pegfilgrastim on severe neutropenia in cancer patients receiving myelosuppressive chemotherapy; efficacy studies in humans for acute radiation syndrome were not conducted for ethical and feasibility reasons. In animal studies, pegfilgrastim significantly increased 60-day survival in irradiated non-human primates (91% vs. 48%; p = 0.0014). Dosing in pediatric patients weighing less than 45 kg is based on population modeling and simulation analysis.

Specific guidelines for dosage adjustments in hepatic impairment are not available; the effect of hepatic insufficiency on the pharmacokinetics of pegfilgrastim has not been evaluated.

A pegfilgrastim dose adjustment is not necessary in patients with renal impairment. Renal dysfunction including end-stage renal disease did not affect the pharmacokinetics of pegfilgrastim in a study of 30 subjects. [63726] [62397] [63242]

Abemaciclib: (Major) Do not administer abemaciclib for at least 48 hours after the last dose of colony stimulating factors, if required. Hematologic toxicities should also be resolved to grade 2 or less prior to resuming treatment with abemaciclib.
Aldesleukin, IL-2: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert their toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Alemtuzumab: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Alpha interferons: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Altretamine: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Antimetabolites: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Betibeglogene Autotemcel: (Major) Avoid administration of pegfilgrastim for 21 days after betibeglogene autotemcel infusion.
Bexarotene: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Busulfan: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert their toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Clofarabine: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Cyclophosphamide: (Minor) Use caution if cyclophosphamide is used concomitantly with pegfilgrastim; reports suggest an increased risk of pulmonary toxicity in patients treated with cytotoxic chemotherapy that includes cyclophosphamide and G-CSF or GM-CSF.
Dacarbazine, DTIC: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Ibritumomab Tiuxetan: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Lithium: (Moderate) Lithium prompts the release of neutrophils and should be used with caution during filgrastim therapy. White blood cell counts above 100,000 cells/mm3 represent a medical emergency because of the risk of serious adverse effects such as brain infarction, respiratory failure, intracranial hemorrhage, retinal hemorrhage, myocardial infarction, and acute limb ischemia. Patients receiving lithium and filgrastim or pegfilgrastim should have more frequent monitoring of WBC counts.
Methotrexate: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert their toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Mitoxantrone: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Natural Antineoplastics: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Nelarabine: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert their toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Procarbazine: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Purine analogs: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert their toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Temozolomide: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert their toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Thiotepa: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert their toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Tositumomab: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Tretinoin, ATRA: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.

Fulphila/Fylnetra/Neulasta/Nyvepria/Pegfilgrastim (E. coli)/Stimufend/UDENYCA/Ziextenzo Subcutaneous Inj Sol: 0.6mL, 6mg

6 mg subcutaneously.

6 mg subcutaneously.

45 kg or greater: 6 mg subcutaneously.31 to 44 kg: 4 mg subcutaneously.

45 kg or greater: 6 mg subcutaneously.31 kg to 44 kg: 4 mg subcutaneously.21 kg to 30 kg: 2.5 mg subcutaneously.10 kg to 20 kg: 1.5 mg subcutaneously.

10 kg to 20 kg: 1.5 mg subcutaneously.less than 10 kg: 0.1 mg/kg subcutaneously.

0.1 mg/kg subcutaneously.

Mechanism of Action: Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein involved in the regulation and production of neutrophils in response to host defense needs. Filgrastim, and thus pegfilgrastim, has the same biologic activity as native G-CSF. The production of G-CSF can be induced by exposure to bacterial cell wall proteins, endotoxin, or proinflammatory cytokines (e.g., interleukin (IL)-1, IL-17, interferon gamma, or tumor necrosis factor). Cells responsible for the production of G-CSF include monocytes and macrophages, endothelial cells, fibroblasts, and bone marrow stromal cells. Normally, G-CSF plasma levels are low or undetectable, but in response to bacterial stimuli, the levels are rapidly and markedly elevated. G-CSF acts on a specific receptor located on hematopoietic progenitor cells and mature neutrophils. G-CSF is also important for the survival of multilineage hematopoietic stem cells, but it cannot sustain their proliferation or differentiation.Administration of exogenous G-CSF results in increased total neutrophil counts, including mature, banded, and precursor neutrophils, without increasing the number of basophils, eosinophils, or monocytes. The rise in neutrophils is due to increased production by the bone marrow and not increased survival of neutrophils. Morphological changes in neutrophils, including densely staining secondary cytoplasmic granules and Dohle bodies, have been observed following administration of exogenous G-CSF. The morphological changes are similar to those seen in neutrophils during infection and are consistent with changes seen in functionally "primed" neutrophils. G-CSF activates polymorphic neutrophils (PMNs) by mobilizing secretory vesicles and inducing the release of granules, which enhance bacterial cytotoxicity. G-CSF also affects selected neutrophil functions including enhanced phagocytic ability, priming of cellular metabolism associated with respiratory burst, antibody-dependent killing, and the increased expression of some functions associated with cell surface antigens.

Pegfilgrastim products are administered subcutaneously. The pharmacokinetic values of pegfilgrastim were nonlinear in 379 cancer patients who received manual subcutaneous injections; the clearance decreased as doses increased. Additionally, the serum clearance was directly related to the number of neutrophils present. Following subcutaneous administration, the half-life of pegfilgrastim ranged from 15 to 80 hours. Pharmacokinetic parameters in healthy subjects were comparable when pegfilgrastim was administered subcutaneously as a manual injection or via the On-body Injector.[62397]

The mean Cmax was 123 +/- 113 ng/mL, the median Tmax was 24 hours (range, 16 to 120 hours), and the mean AUCinf value was 10,000 +/- 11,600 ng x hour/mL following the subcutaneous administration of pegfilgrastim 6 mg given no sooner than 24 hours after the completion of chemotherapy (for 4 cycles) in 73 patients with high-risk stage II or stage III/IV breast cancer. Information on the pharmacokinetics of pegfilgrastim in human patients acutely exposed to myelosuppressive doses of radiation is not available. Based on pharmacokinetic data, the AUC of pegfilgrastim 300 mcg/kg in irradiated nonhuman primates is greater than the AUC in humans who received a single dose of pegfilgrastim 6 mg. Based on population modeling and simulation in adults, two 6 mg doses of pegfilgrastim, administered one week apart, produced a clinically relevant effect on the duration of grade 3 and 4 neutropenia; animal data and clinical data in humans suggest a correlation between pegfilgrastim exposure and the duration of severe neutropenia as a predictor of efficacy.[62397]

Retrospective studies in humans indicate that exposure to pegfilgrastim during pregnancy does not result in significant adverse effects on the fetus or neutropenia. However, preterm deliveries have been reported in some patients.[63242] In pregnant rabbits, an increased rate of embryotic death and spontaneous abortion occurred following a pegfilgrastim cumulative dose of about 4-times the recommended human dose. Additionally, decreased fetal weight was observed at pegfilgrastim doses that were approximately equivalent to the recommended human dose. No developmental toxicity was observed in rat offspring following pegfilgrastim doses up to about 10-times the recommended human dose. [63726] [62397] [63242]

Weigh the potential risk to the infant against the potential benefits to the mother prior to initiating pegfilgrastim therapy in a woman who is breast-feeding. It is not known if pegfilgrastim is secreted in human milk or if it has effects on the breast-fed infant or milk production. Other filgrastim products are poorly secreted into breast milk and are not orally absorbed by neonates. [63726] [62397] [63242]