Pegfilgrastim is a leukocyte growth factor that binds to cell surface receptors on hematopoietic cells stimulating proliferation, differentiation, commitment, and end cell functional activation. It is indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation; efficacy for this indication was based on animal data in monkeys. Pegfilgrastim is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia. Pegfilgrastim is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem-cell transplantation. Acute respiratory distress syndrome, fatal splenic rupture, and glomerulonephritis have occurred with pegfilgrastim products.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Subcutaneous Administration
-Pegfilgrastim is available as a single-dose prefilled syringe for manual use, a kit containing an on-body injector (OBI) with a single-dose prefilled syringe (Neulasta, Udenyca), and a single-dose prefilled autoinjector (Udenyca).
-Read and become familiar with the manufacturer's "Instructions for Use" prior to preparing or injecting the prefilled syringe or autoinjector or prior to preparing and applying the OBI.
-Do not use the single-use prefilled syringe intended for manual injection with the OBI or the patient will receive less than the recommended dose; additionally, do not fill the OBI with any other drug.
-Do not use the single-use prefilled syringe contained in the OBI 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:
-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; refer to the manufacturer's package insert for recommendations on how long syringes may be kept at room temperature before they need to be discarded.
-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).
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.
-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 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).
On-Body Injector (OBI):
-Apply the OBI on the patient after chemotherapy completes; report problems to Amgen at 1-800-772-6436 for Neulasta Onpro or Coherus at 1-800-483-3692 for Udenyca Onbody.
-The OBI is not recommended for use in patients acutely exposed to radiation; additionally, the OBI has not been studied in pediatric patients.
-Do not expose the OBI to medical imaging studies (e.g., X-ray scan, MRI, CT scan and ultrasound), radiation treatment, and oxygen rich environments such as hyperbaric chambers.
-Allow kits to warm up to room temperature 30 minutes before application; discard any kits kept at room temperature for more than 12 hours.
Preparation:
-Locate the medicine port; insert the single-use, prefilled syringe (provided in the kit) needle at 90 degrees and slowly fill the OBI with pegfilgrastim.
-After filling, the Neulasta OBI needs to be placed on the patient within 3 minutes after the activation light starts to flash.
Application:
-Clean the application site with alcohol and apply the OBI to dry, intact, and oil-free skin on the abdomen (horizontally with light facing up and visible to the patient) or back or the arm (vertically with light facing down toward the elbow).
-Ensure the adhesive does not bend or curl while applying the OBI to the skin.
-Do not use other materials to hold the OBI in place that could cover visual indicators or compress the OBI against the patient's skin.
-Once applied, the OBI should be kept at temperatures between 41 and 104 degrees F (5 and 40 degrees C).
-The OBI should remain dry starting at 24 hours after placement (approximately 3 hours before drug delivery begins).
Subcutaneous Injection Using OBI:
-The OBI will deliver the pegfilgrastim dose approximately 27 hours after placement. The Neulasta OBI delivers the dose over 45 minutes; the Udenyca OBI delivers the dose over 5 minutes.
-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 OBI failure or leakage, a new dose using the single prefilled syringe for manual use should be administered as soon as possible.
In a randomized, double-blind study, bone pain (31% vs. 26%) and extremity pain (9% vs. 4%) occurred more often in breast cancer patients who received a single injection of pegfilgrastim (n = 467) compared with placebo (n = 461) on day 2 following docetaxel 100 mg/m2 IV given every 3 weeks. In a trial of 37 pediatric patients with sarcoma, bone pain was the most common adverse reaction following pegfilgrastim administration.
Leukocytosis and thrombocytopenia have been reported in patients who received pegfilgrastim products. Monitor complete blood counts during pegfilgrastim therapy. In a pooled analysis of 7 randomized studies (n = 932), leukocytosis (WBC count greater than 100 x 109 cells/L) occurred in less than 1% of patients with non-myeloid malignancies who received a single injection of pegfilgrastim (100 micrograms/kg or 6 mg) following myelosuppressive chemotherapy. No leukocytosis-related complications were reported.
Serious allergic reactions (e.g., anaphylactoid reactions, rash, generalized erythema, flushing, and urticaria) have been reported in postmarketing surveillance of pegfilgrastim. Most allergic reactions occurred with the first dose and some reactions recurred days after treatment with anti-allergy medications. Permanently discontinue pegfilgrastim in patients who experience a serious allergic reaction. Contact dermatitis and local skin reactions (e.g., rash and pruritus) were also reported in postmarketing surveillance of the pegfilgrastim on-body injector (OBI). Local skin reactions may be a hypersensitivity reaction to the acrylic adhesive from the OBI.
Acute respiratory distress syndrome (ARDS) has been reported in postmarketing surveillance of pegfilgrastim products. Evaluate patients who have signs (e.g., lung infiltrates) or who develop symptoms (e.g., fever, respiratory distress) of ARDS. Discontinue pegfilgrastim if a patient is diagnosed with ARDS.
Splenic rupture and splenomegaly have been reported in postmarketing surveillance of pegfilgrastim products; some cases of splenic rupture resulted in death. Evaluate patients who have left upper abdominal or shoulder pain for evidence of splenomegaly or splenic rupture.
Antibody formation to pegfilgrastim was evaluated using a BIAcore assay that had an approximate limit of detection of 500 ng/mL. Pre-existing binding antibodies were detected in about 6% of patients (n = 51 of 849) with metastatic breast cancer. Binding antibodies developed in less than 1% of patients (n = 4 of 521) who were negative at baseline; none of these patients had evidence of neutralizing antibodies.
Sickle-cell crisis has been reported in patients with sickle cell disease in postmarketing surveillance of pegfilgrastim products; some cases were fatal. Monitor patients with sickle cell disease for symptoms of a sickle-cell crisis such as pain or difficulty breathing. Discontinue pegfilgrastim if sickle cell crisis occurs.
Injection site reaction, Sweet's syndrome (febrile neutrophilic dermatosis), cutaneous vasculitis, and alveolar hemorrhage have been reported in postmarketing surveillance of pegfilgrastim products. Application site reaction (e.g., bleeding, pain, discomfort, bruising, and erythema) has been reported with the use of the pegfilgrastim on-body injector.
Glomerulonephritis has been reported in postmarketing surveillance of pegfilgrastim products. Signs of glomerulonephritis include azotemia, hematuria, and proteinuria; a renal biopsy may confirm the diagnosis. Consider holding a dose or a dose reduction if a patient develops glomerulonephritis caused by pegfilgrastim.
Capillary leak syndrome has been reported in postmarketing surveillance of pegfilgrastim products. Signs of capillary leak syndrome include hypotension, hypoalbuminemia, hemoconcentration, and edema. Closely monitor and promptly treat patients who develop signs or symptoms of capillary leak syndrome; treatment in an intensive care setting may be required.
In postmarketing surveillance, aortitis has been reported in who received pegfilgrastim; this adverse event may occur in the first week of therapy. Signs and symptoms of aortitis may include fever, abdominal pain, malaise, back pain, and increased inflammatory markers (e.g., C-reactive protein and white blood cell count). Discontinue pegfilgrastim if aortitis is suspected.
New primary malignancy including myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) has been reported in postmarketing surveillance of patients with lung or breast cancer who received pegfilgrastim in conjunction with chemotherapy and/or radiotherapy. Monitor these patients for signs and symptoms of MDS and AML.
Pegfilgrastim is contraindicated for use in patients with a granulocyte stimulating factor hypersensitivity. Serious allergic reactions (e.g., anaphylaxis) have been reported. Most reactions occurred with the first dose and some reactions recurred days after treatment with anti-allergy medications. Permanently discontinue pegfilgrastim products in patients who experience a serious allergic reaction. On-body injectors may cause severe, localized skin reactions in patients who have a hypersensitivity to acrylic adhesives.
Use pegfilgrastim products with caution in patients with sickle cell disease or sickle cell trait because severe sickle cell crises have been reported in this patient population; some cases were fatal. Monitor patients with sickle cell disease for symptoms of sickle cell crises such as pain or difficulty breathing. Discontinue pegfilgrastim if sickle cell crisis occurs.
Pegfilgrastim stimulates the production of hematopoietic stem cells and it may act as a growth factor for myeloid cells in myeloid malignancies and myelodysplasia. Additionally, increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. This should be considered when interpreting bone-imaging results. Patients with lung cancer or breast cancer who received pegfilgrastim in conjunction with chemotherapy and/or radiotherapy may be at increased risk for developing a new primary malignancy including myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML); monitor these patients for signs and symptoms of MDS and AML.
Leukocytosis (WBC count greater than 100 x 109 cells/L) and thrombocytopenia have been reported with pegfilgrastim use. Monitor complete blood counts during therapy with pegfilgrastim products.
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. 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.
Patients should avoid driving or operating machinery during hours 26 through 29 following the application of an on-body injector (OBI). This timeframe includes the dose delivery period and 1 hour after. Patients should have a caregiver nearby for the first dose and if the OBI is placed on the back of the patient's arm.
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.
For chemotherapy-induced neutropenia prophylaxis, to decrease the incidence of febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive chemotherapy associated with a clinically significant incidence of febrile neutropenia:
Subcutaneous dosage:
Note: On-body injector products have not been studied in pediatric patients.
Adults, Adolescents, and Children weighing 45 kg or more: 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. 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. 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).
Children and Adolescents weighing 31 to 44 kg: 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).
Children weighing 21 to 30 kg: 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).
Infants and Children weighing 10 to 20 kg: 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).
Neonates and Infants weighing less than 10 kg: 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).
For the treatment of acute radiation exposure, to increase survival, in patients who receive myelosuppressive doses of radiation:
NOTE: The on-body injector is not recommended for use in patients with acute radiation exposure.
NOTE: Pegfilgrastim is designated as an orphan drug by the FDA for this indication.
Subcutaneous dosage:
Adults, Adolescents, and Children weighing 45 kg or more: 6 mg subcutaneously once, followed by a second dose of 6 mg subcutaneously 1 week later, for a total of 2 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).
Children and Adolescents weighing 31 to 44 kg: 4 mg subcutaneously once, followed by a second dose of 4 mg subcutaneously 1 week later, for a total of 2 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.
Children and Adolescents weighing 21 to 30 kg: 2.5 mg subcutaneously once, followed by a second dose of 2.5 mg subcutaneously 1 week later, for a total of 2 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.
Infants and Children weighing 10 to 20 kg: 1.5 mg subcutaneously once, followed by a second dose of 1.5 mg subcutaneously 1 week later, for a total of 2 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.
Neonates and Infants weighing less than 10 kg: 0.1 mg/kg subcutaneously once, followed by a second dose of 0.1 mg/kg subcutaneously 1 week later, for a total of 2 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.
Maximum Dosage Limits:
-Adults
6 mg subcutaneously.
-Geriatric
6 mg subcutaneously.
-Adolescents
45 kg or greater: 6 mg subcutaneously.
31 to 44 kg: 4 mg subcutaneously.
-Children
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.
-Infants
10 kg to 20 kg: 1.5 mg subcutaneously.
less than 10 kg: 0.1 mg/kg subcutaneously.
-Neonates
0.1 mg/kg subcutaneously.
Patients with Hepatic Impairment Dosing
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.
Patients with Renal Impairment Dosing
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.
*non-FDA-approved indication
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.
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.
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 granulocyte-colony stimulating factors 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.
Cladribine: (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.
Exagamglogene autotemcel: (Major) Avoid administration of granulocyte-colony stimulating factors for 21 days after exagamglogene autotemcel infusion.
Fludarabine: (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.
Hydroxyurea: (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.
Interferon Alfa-2b: (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.
Interferon Alfa-n3: (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.
Lovotibeglogene autotemcel: (Major) Avoid administration of granulocyte-colony stimulating factors for 21 days after lovotibeglogene autotemcel infusion.
Mercaptopurine, 6-MP: (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.
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.
Pegaspargase: (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.
Peginterferon Alfa-2a: (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.
Peginterferon Alfa-2b: (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.
Pentostatin: (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.
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.
Ropeginterferon alfa-2b: (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.
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.
Thioguanine, 6-TG: (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.
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.
Vinblastine: (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.
Vincristine Liposomal: (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.
Vincristine: (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.
Vinorelbine: (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.
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.
-Route-Specific Pharmacokinetics
Subcutaneous Route
The mean Cmax was 123 +/- 113 nanograms (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.
-Special Populations
Renal Impairment
In a study of 30 adult patients with cancer, pharmacokinetic parameters for pegfilgrastim were unaffected by varying degrees of renal dysfunction including end-stage renal disease.
Pediatrics
Following the subcutaneous administration of pegfilgrastim 100 micrograms (mcg)/kg in sarcoma patients aged 0 to 5 years (n = 11), 6 to 11 years (n = 10), and 12 to 21 years (n =13), the mean AUC values were 47.9 +/- 22.5 mcg x hour/mL, 22 +/- 13.1 mcg x hour/mL, and 29.3 +/- 23.2 mcg x hour/mL, respectively. Additionally, the mean terminal elimination half-lives were 30.1 +/- 38.2 hours, 20.2 +/- 11.3 hours, and 21.2 +/- 16 hours, respectively. Based on population modeling and simulation, the pediatric exposure of pegfilgrastim, administered at the recommended weight-based dosage for 2 doses given 1 week apart, was comparable to the exposure in adults who received 2 doses of pegfilgrastim 6 mg 1 week apart.
Geriatric
Age (65 years or older) did not affect the pharmacokinetic parameters of pegfilgrastim.
Gender Differences
Gender did not affect the pharmacokinetic parameters of pegfilgrastim.
Obesity
Patients with a higher body weight had increased pegfilgrastim systemic exposure following a dose normalized for body weight.