Tbo-filgrastim 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 decrease the duration of neutropenia in patients aged 1 month and older with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia. Acute respiratory distress syndrome, fatal splenic rupture, and glomerulonephritis have occurred with filgrastim products, including tbo-filgrastim.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Wash the area with soap and water if tbo-filgrastim gets on skin. If tbo-filgrastim gets in the eyes, thoroughly flush the exposed eye/eyes with water.
Route-Specific Administration
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Subcutaneous Administration
-Tbo-filgrastim is available as prefilled syringes (300 mcg/0.5 mL; 480 mcg/0.8 mL) or vials (300 mcg/mL; 480 mcg/1.6 mL); note that the tbo-filgrastim concentration is different for syringes and vials.
-Administer tbo-filgrastim at least 24 hours before or 24 hours after chemotherapy.
-Patient or caregiver may administer after being properly trained on storage, preparation, and administration technique; refer to the Instructions for Use provided by manufacturer.
-Do not shake vials or prefilled syringes.
-Store vials or prefilled syringes in the refrigerator between 2 to 8 degrees C (36 to 46 degrees F) in the carton. Protect from light and do not freeze.
-Prior to use, allow tbo-filgrastim vials or prefilled syringes to reach room temperature for at least 30 minutes; discard any vial or prefilled syringe exposed to room temperature for more than 5 days.
-Products are for single-use; do not re-enter the vial or save unused drug for later administration.
Subcutaneous Injection:
-If using the vial product (300 mcg/mL), withdraw the appropriate tbo-filgrastim dose from the vial into a syringe.
-Inject subcutaneously in a recommended subcutaneous 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).
Splenic rupture has been reported in patients who received filgrastim products; some cases were fatal. Hold tbo-filgrastim and evaluate patients who have left upper abdominal pain or shoulder pain for evidence of splenomegaly or splenic rupture.
Fever occurred in 8% of pediatric patients (median age, 9.2 years; range, 1.4 to 15.9 years) with solid tumors who received tbo-filgrastim after myelosuppressive chemotherapy in a clinical trial (n = 50).
Acute respiratory distress syndrome (ARDS) has been reported in patients who received filgrastim products. Signs and symptoms may include fever, dyspnea or fast breathing, lung infiltrates, or respiratory distress. Evaluate patients who develop symptoms of ARDS. Discontinue tbo-filgrastim in patients with confirmed ARDS. Alveolar hemorrhage/bleeding manifesting as pulmonary infiltrates and hemoptysis requiring hospitalization have been reported in healthy donors who received filgrastim products for peripheral blood progenitor cell (PBPC) mobilization, an off-label use of tbo-filgrastim. Hemoptysis resolved with filgrastim discontinuation.
Sickle-cell crisis has been reported in patients with sickle cell disease/disorder who received filgrastim products; some cases were fatal. Discontinue tbo-filgrastim in patients who develop a sickle-cell crisis during therapy.
Bone pain occurred more often in adult patients who received tbo-filgrastim compared with placebo (3.4% vs. 1.4%) in clinical trials. Extremity pain occurred in 6% of pediatric patients (median age, 9.2 years; range, 1.4 to 15.9 years) with solid tumors who received tbo-filgrastim after myelosuppressive chemotherapy in a clinical trial (n = 50).
Leukocytosis (defined as a white blood cell (WBC) count greater than 100,000 cells/mm3) has been reported in less than 1% of patients with non-myeloid malignancies who received tbo-filgrastim in clinical trials. There were no complications reported as a result of leukocytosis. Monitor complete blood counts at least twice weekly during tbo-filgrastim therapy. Discontinue therapy if the absolute neutrophil count (ANC) exceeds 10,000 cells/mm3 after the chemotherapy-induced ANC nadir has occurred. WBC counts of 100,000 cells/mm3 or more have been reported in about 2% of patients who received filgrastim products at a dose of 5 mcg/kg daily. Discontinuing a filgrastim product results in a 50% decrease in circulating neutrophils within 1 to 2 days with a return to pretreatment levels in 1 to 7 days.
Capillary leak syndrome has been reported in patients who received filgrastim products; some cases were severe and life-threatening. Symptoms include hypotension, hypoalbuminemia, edema, and hemoconcentration. Closely monitor patients who develop symptoms of capillary leak syndrome administer standard medical treatment.
Serious allergic reactions/hypersensitivity including anaphylactoid reactions, angioedema, allergic/contact dermatitis, rash (unspecified), pruritus, and urticaria may occur with tbo-filgrastim therapy. Permanently discontinue tbo-filgrastim in patients who develop a serious allergic reaction. Some reactions may happen with the first exposure. The use of antihistamines, steroids, bronchodilators, and/or epinephrine may reduce the severity of the reaction. Permanently discontinue tbo-filgrastim in patients who experience a serious allergic reaction.
Glomerulonephritis has been reported in patients who received filgrastim products. Signs and symptoms may include azotemia, hematuria, and proteinuria. A renal biopsy may confirm a diagnosis. Consider holding therapy or a dose reduction if glomerulonephritis is attributed to tbo-filgrastim; signs and symptoms usually resolve following a dose reduction or drug discontinuation.
Myalgia was reported in adult patients with cancer who received tbo-filgrastim in clinical trials.
Headache was reported in adult patients with cancer who received tbo-filgrastim in clinical trials. Headache occurred in 6% of pediatric patients (median age, 9.2 years; range, 1.4 to 15.9 years) with solid tumors who received tbo-filgrastim after myelosuppressive chemotherapy in a clinical trial (n = 50).
Thrombocytopenia was reported in adult patients with cancer who received tbo-filgrastim in clinical trials. Thrombocytopenia occurred in 34% of pediatric patients (median age, 9.2 years; range, 1.4 to 15.9 years) with solid tumors who received tbo-filgrastim after myelosuppressive chemotherapy in a clinical trial (n = 50).
Cutaneous vasculitis occurred in adult patients with cancer who received tbo-filgrastim in clinical trials. Sweet's syndrome (acute febrile neutrophilic dermatosis) has been reported in postmarketing surveillance of tbo-filgrastim.
Asthenia has been reported in postmarketing surveillance of tbo-filgrastim.
Vomiting occurred in adult patients with cancer who received tbo-filgrastim in clinical trials. Diarrhea has been reported in postmarketing surveillance of tbo-filgrastim. Additionally, diarrhea occurred in 6% of pediatric patients (median age, 9.2 years; range, 1.4 to 15.9 years) with solid tumors who received tbo-filgrastim after myelosuppressive chemotherapy in a clinical trial (n = 50).
Fatigue has been reported in postmarketing surveillance of tbo-filgrastim.
Antibody formation to filgrastim in 1.4% of patients who received tbo-filgrastim or other filgrastim products. Cytopenias caused by an antibody response have rarely been reported with other recombinant growth factors.
Aortitis has been reported in patients who received other filgrastim products; 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 tbo-filgrastim if aortitis is suspected.
New primary malignancy, including myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML), has been reported in breast and lung cancer patients who received filgrastim in conjunction with cytotoxic chemotherapy and/or radiotherapy. Monitor these patients for signs and symptoms of MDS and AML. Additionally, cytogenetic abnormalities, MDS, and AML were reported in postmarketing surveillance in patients with congenital neutropenia who received tbo-filgrastim.
Tbo-filgrastim is contraindicated for use in patients with a granulocyte stimulating factor hypersensitivity. Serious allergic reactions (e.g., anaphylaxis) may occur with tbo-filgrastim use, including at the time of first exposure. The use of antihistamines, steroids, bronchodilators, and/or epinephrine may reduce the severity of the reaction. Permanently discontinue tbo-filgrastim in patients who experience a serious allergic reaction.
Tbo-filgrastim stimulates the production of hematopoietic stem cells, primarily neutrophils, and it may act as a growth factor for myeloid cells in myeloid malignancies. Therefore, tbo-filgrastim is not indicated for use in patients with leukemia or myelodysplastic syndrome (MDS). 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 congenital neutropenia who receive tbo-filgrastim may be at increased risk of developing cytogenetic abnormalities, MDS, and acute myelogenous leukemia (AML). Monitor these patients for signs and symptoms of MDS/AML. Because the risk of developing a myeloid malignancy is increased in patients with abnormal cytogenetics or MDS, perform a risk/benefit analysis of tbo-filgrastim use in patients with congenital neutropenia who develop abnormal cytogenetics or myelodysplasia.
Use tbo-filgrastim with caution in patients with sickle cell disease; sickle cell crisis has been reported in patients with sickle cell disease who received granulocyte colony-stimulating factor, including filgrastim products; some cases were fatal. Discontinue tbo-filgrastim in patients who develop a sickle cell crisis during therapy.
Leukocytosis (white blood cell count greater than 100,000 cells/mm3) has been reported with tbo-filgrastim use. Monitor complete blood counts at least twice weekly during tbo-filgrastim therapy. Discontinue therapy if the absolute neutrophil count (ANC) exceeds 10,000 cells/mm3 after the chemotherapy-induced ANC nadir has occurred.
Avoid the simultaneous use of tbo-filgrastim with chemotherapy and radiation therapy due to the potential sensitivity of rapidly dividing myeloid cells. New primary malignancy, specifically, myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML), has occurred in patients with breast cancer or lung cancer who received tbo-filgrastim in conjunction with chemotherapy and/or radiation therapy. Monitor this patient population for signs and symptoms of MDS/AML.
Use tbo-filgrastim during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus. In animal studies in pregnant rabbits, a systemic tbo-filgrastim exposure of 50 to 90-times the human exposure (at the recommended human dose) resulted in an increased incidence in spontaneous abortion and fetal malformations.
It is not known if tbo-filgrastim is secreted in human milk or if it has effects on the breast-fed child or on milk production. With another filgrastim product, filgrastim was detected in human milk for up to 3 days after administration. Due to a potential for serious adverse reactions in the breast-fed child (e.g., splenic rupture, acute respiratory distress syndrome, and serious allergic reactions), avoid breast-feeding during tbo-filgrastim therapy and for 2 weeks after the last dose.
For chemotherapy-induced neutropenia prophylaxis to reduce the duration of severe neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive chemotherapy associated with a clinically significant incidence of febrile neutropenia:
Subcutaneous dosage:
Adults: 5 mcg/kg subcutaneously daily until the expected neutrophil nadir is passed and the neutrophil count has recovered to the normal range. Administer the first dose at least 24 hours after myelosuppressive chemotherapy. Do not administer tbo-filgrastim within the 24 hours before chemotherapy. The duration of severe neutropenia was significantly shorter in chemotherapy-naive patients with high-risk stage breast cancer who received tbo-filgrastim compared with placebo (1.1 days vs. 3.8 days; p less 0.0001) following chemotherapy with doxorubicin and docetaxel in a randomized trial (n = 348).
Adolescents, Children, and Infants: 5 mcg/kg subcutaneously daily until the expected neutrophil nadir is passed and the neutrophil count has recovered to the normal range. Administer the first dose at least 24 hours after myelosuppressive chemotherapy. Do not administer tbo-filgrastim within the 24 hours before chemotherapy. Use of tbo-filgrastim in pediatric patients 1 month and older is supported by evidence from clinical studies in adult patients.
Maximum Dosage Limits:
-Adults
5 mcg/kg per day subcutaneously.
-Geriatric
5 mcg/kg per day subcutaneously.
-Adolescents
5 mcg/kg per day subcutaneously.
-Children
5 mcg/kg per day subcutaneously.
-Infants
5 mcg/kg per day subcutaneously.
-Neonates
Safety and efficacy not established.
Patients with Hepatic Impairment Dosing
Tbo-filgrastim use has not been evaluated in patients with hepatic impairment. Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Tbo-filgrastim use has not been evaluated in patients with moderate and severe renal impairment (creatinine clearance less than 60 mL/min). Specific guidelines for dosage adjustments in renal impairment are not available; it appears no dosage adjustments are needed.
*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) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Alpha interferons: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Antimetabolites: (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.
Betibeglogene Autotemcel: (Major) Avoid administration of granulocyte-colony stimulating factors for 21 days after betibeglogene autotemcel infusion.
Bexarotene: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Chlorambucil: (Major) Because antineoplastic agents exert their toxic effects against rapidly growing cells, such as hematopoietic progenitor cells, filgrastim, is contraindicated for use in patients in the period 24 hours before through 24 hours after treatment with cytotoxic chemotherapy.
Cladribine: (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.
Clofarabine: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Cyclophosphamide: (Minor) Use caution if cyclophosphamide is used concomitantly with filgrastim, G-CSF; reports suggest an increased risk of pulmonary toxicity in patients treated with cytotoxic chemotherapy that includes cyclophosphamide and G-CSF.
Docetaxel: (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.
Estramustine: (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.
Exagamglogene autotemcel: (Major) Avoid administration of granulocyte-colony stimulating factors for 21 days after exagamglogene autotemcel infusion.
Fludarabine: (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.
Hydroxyurea: (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.
Ibritumomab Tiuxetan: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Interferon Alfa-2b: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Interferon Alfa-n3: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or 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.
Lomustine, CCNU: (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.
Lovotibeglogene autotemcel: (Major) Avoid administration of granulocyte-colony stimulating factors for 21 days after lovotibeglogene autotemcel infusion.
Mercaptopurine, 6-MP: (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.
Methotrexate: (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.
Natural Antineoplastics: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or 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.
Paclitaxel: (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) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Peginterferon Alfa-2a: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Peginterferon Alfa-2b: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Pentostatin: (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.
Ropeginterferon alfa-2b: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Tretinoin, ATRA: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Vinblastine: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Vincristine Liposomal: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Vincristine: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Vinorelbine: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Tbo-filgrastim is a human granulocyte colony-stimulating factor (G-CSF) manufactured by recombinant DNA technology using the bacterium strain E coli K802. It works by binding to G-CSF receptors and stimulating the proliferation of neutrophils. G-CSF stimulates the differentiation of leukocytes, which increases neutrophil counts and activity.
Tbo-filgrastim is administered subcutaneously. Following a subcutaneous dose of tbo-filgrastim 5 mcg/kg, the median serum elimination half-life was 3 to 3.5 hours. Tbo-filgrastim clearance is dependent on granulocyte colony stimulating factor-mediated clearance which can be saturated by high serum concentrations of tbo-filgrastim and diminished in neutropenia.
The time to the maximum absolute neutrophil count (ANC) was between 3 and 5 days and returned to baseline by 21 days after chemotherapy completion. Doubling the tbo-filgrastim subcutaneous dose from 5 to 10 mcg/kg resulted in a 16% to 19% increase in the maximum ANC value and a 33% to 36% increase in the AUC value for the ANC.
-Route-Specific Pharmacokinetics
Subcutaneous Route
The absolute bioavailability is 33% following a tbo-filgrastim 5 mcg/kg subcutaneous dose. Tbo-filgrastim exhibits nonlinear pharmacokinetics. Doubling the dose from 5 to 10 mcg/kg resulted in an approximately 2.5-fold increase in the Cmax value and a 3-fold increase in the AUC value. In adult patients enrolled in 3 studies, the geometric mean Cmax values were 20 to 31 ng/mL (coefficient of variation (CV), 24% to 65%) at a median Tmax of 4 to 6 hours following a tbo-filgrastim 5 mcg/kg subcutaneous dose. In this analysis, the geometric mean AUC(0 to 12 hours) values ranged from 151 to 227 ng/mL x hour (CV, 24% to 60%). Accumulation did not occur after multiple doses of tbo-filgrastim.
-Special Populations
Renal Impairment
Mild renal impairment (creatinine clearance of 60 to 89 mL/min) does not affect the pharmacokinetic (PK) parameters of tbo-filgrastim; it is not known if the PK parameters of tbo-filgrastim are affected by moderate or severe renal impairment.
Gender Differences
Gender does not affect the pharmacokinetic parameters of tbo-filgrastim.