Granix

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Granix

Classes

Colony-stimulating Factors

Administration

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.

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).

Adverse Reactions
Severe

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

Moderate

thrombocytopenia / Delayed / 0-34.0
bone pain / Delayed / 3.4-3.4
antibody formation / Delayed / 1.4-1.4
splenomegaly / Delayed / Incidence not known
bleeding / Early / Incidence not known
hemoptysis / Delayed / Incidence not known
dyspnea / Early / Incidence not known
hypoalbuminemia / Delayed / Incidence not known
hypotension / Rapid / Incidence not known
edema / Delayed / Incidence not known
contact dermatitis / Delayed / Incidence not known
hematuria / Delayed / Incidence not known
proteinuria / Delayed / Incidence not known

Mild

fever / Early / 0-8.0
headache / Early / 0-6.0
diarrhea / Early / 0-6.0
leukocytosis / Delayed / 0-1.0
abdominal pain / Early / Incidence not known
rash / Early / Incidence not known
pruritus / Rapid / Incidence not known
urticaria / Rapid / Incidence not known
myalgia / Early / Incidence not known
asthenia / Delayed / Incidence not known
vomiting / Early / Incidence not known
fatigue / Early / Incidence not known
malaise / Early / Incidence not known
back pain / Delayed / Incidence not known

Common Brand Names

Granix

Dea Class

Rx

Description

Granulocyte colony-stimulating factor
Used to decrease the duration of neutropenia in patients with nonmyeloid malignancies receiving myelosuppressive chemotherapy associated with a clinically significant incidence of febrile neutropenia
Acute respiratory distress syndrome, fatal splenic rupture, and glomerulonephritis may occur

Dosage And Indications
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.

Dosing Considerations
Hepatic Impairment

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.

Renal Impairment

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.

Drug Interactions

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) 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.
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.
Altretamine: (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.
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 filgrastim 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.
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.
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.
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.
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.
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.
Tositumomab: (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.

How Supplied

Granix Subcutaneous Inj Sol: 0.5mL, 0.8mL, 1mL, 1.6mL, 300mcg, 480mcg

Maximum Dosage
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.

Mechanism Of Action

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.

Pharmacokinetics

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.

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.

Pregnancy And Lactation
Pregnancy

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.

Use tbo-filgrastim with caution women who are breast-feeding. It is not known if tbo-filgrastim is secreted in human milk or if it has effects on the breast-fed infant or on milk production. With another filgrastim product, filgrastim was detected in human milk for up to 3 days after administration.