Neupogen

Colony-stimulating Factors

Filgrastim may be administered as a subcutaneous injection, a short intravenous (IV) infusion, or as a continuous IV infusion.
Administer filgrastim at least 24 hours before or 24 hours after chemotherapy.
Do not shake vials or prefilled syringes.
Store vials or prefilled syringes in the refrigerator (2 to 8 degrees C; 36 and 46 degrees F) in the carton. Protect from light.
Avoid freezing filgrastim products. If frozen (Neupogen, Nivestym, or Zarxio only), thaw in the refrigerator; throw away if the product has been frozen more than once.
Prior to use, allow filgrastim vials or prefilled syringes to reach room temperature for least 30 minutes; discard any vial or prefilled syringe exposed to room temperature for more than 24 hours.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Products are for single-use; do not re-enter the vial or save unused drug for later administration.

Dilute prior to intravenous (IV) use.
Dilution
After calculating/selecting the appropriate dose, dilute the filgrastim vial (concentration of 300 mcg/mL) in 5% Dextrose Injection to a final concentration of 5 mcg/mL or more. Do NOT dilute with 0.9% Sodium Chloride Injection; the product may precipitate.
Use a glass bottle, a polyvinyl chloride (PCV) or polyolefin IV bag, or a polypropylene syringe as a container for the diluted solution.
To protect the absorption of filgrastim to the plastic container in diluted solutions at concentrations of 5 to 15 mcg/mL, add albumin to a final concentration of 2 mg/mL.
Storage after dilution: Diluted filgrastim IV solutions may be stored at room temperature for up to 24 hours (Neupogen, Nivestym, or Zarxio) or up to 4 hours (Releuko); the total storage time includes the infusion time.
IV Infusion
Administer the diluted IV infusion over 15 to 30 minutes or as a continuous IV infusion given over 24 hours.

Single-dose vials or prefilled-syringes may be used for subcutaneous injections.
Patient or caregiver may administer after being properly trained on storage, preparation, and administration technique. Follow instructions for use provided by manufacturer.
No dilution is necessary.
Subcutaneous Injection Using Prefilled Syringe
Do not activate the needle guard prior to injection; pull the needle cover straight off.
The Nivestym, Zarxio, and Releuka prefilled syringes are not designed to administer doses less than 0.3 mL (180 mcg).
Inject filgrastim 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).
Do not recap the needle; slide the needle guard over the needle until the needle is completely covered and the needle guard clicks into place.
Subcutaneous Injection Using Single-Use Vials
Withdraw the contents of the filgrastim vial into a syringe.
Inject filgrastim subcutaneously 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).

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

thrombocytopenia / Delayed / 5.0-38.0
bone pain / Delayed / 5.0-30.0
dyspnea / Early / 0-13.0
chest pain (unspecified) / Early / 5.0-13.0
antibody formation / Delayed / 3.0-3.0
splenomegaly / Delayed / 5.0
anemia / Delayed / 5.0
erythema / Early / 2.0
hypertension / Early / 5.0
peripheral edema / Delayed / 5.0
constipation / Delayed / 2.0
wheezing / Rapid / Incidence not known
hemoptysis / Delayed / Incidence not known
bleeding / Early / Incidence not known
hypoxia / Early / Incidence not known
hematuria / Delayed / Incidence not known
proteinuria / Delayed / Incidence not known
edema / Delayed / Incidence not known
hypoalbuminemia / Delayed / Incidence not known
hypotension / Rapid / Incidence not known
osteoporosis / Delayed / Incidence not known

fever / Early / 5.0-48.0
nausea / Early / 43.0-43.0
back pain / Delayed / 2.0-15.0
cough / Delayed / 0-14.0
rash / Early / 5.0-14.0
dizziness / Early / 14.0-14.0
headache / Early / 10.0-10.0
arthralgia / Delayed / 5.0-9.0
leukocytosis / Delayed / 2.0-2.0
maculopapular rash / Early / 2.0
alopecia / Delayed / 5.0
asthenia / Delayed / 5.0
fatigue / Early / 20.0
malaise / Early / 5.0
muscle cramps / Delayed / 5.0
musculoskeletal pain / Early / 5.0
hypoesthesia / Delayed / 5.0
vomiting / Early / 5.0
anorexia / Delayed / 5.0
diarrhea / Early / 2.0
epistaxis / Delayed / 2.0
infection / Delayed / 5.0
insomnia / Early / 5.0
abdominal pain / Early / Incidence not known

Neupogen, Nivestym, Releuko, Zarxio

Rx

Granulocyte colony-stimulating factor
Used to reduce the duration of neutropenia and incidence of infection in patients receiving myelosuppressive chemotherapy or myeloablative chemotherapy followed by bone marrow transplant; also used for the mobilization of peripheral blood progenitor cells for leukapheresis, for the treatment of severe chronic neutropenia, and to improve survival following acute radiation exposure
Acute respiratory distress syndrome, fatal splenic rupture, and glomerulonephritis have been reported

6 mcg/kg subcutaneously twice daily initially. Individualize the dosage to maintain clinical benefit based on patient clinical course and absolute neutrophil count (ANC). In a postmarketing surveillance study in 731 patients (adults, n = 302; pediatric patients, n = 429), the median filgrastim dose was 6 mcg/kg/day. Rarely, doses of 100 mcg/kg/day or more have been required. The starting dose for congenital neutropenia was 11.5 mcg/kg/day (based on actual body weight) given subcutaneously in 2 divided doses in a randomized trial in patients with chronic severe neutropenia (n = 123; median age of 12.1 years; range, 7 months to 76 years). In this study, the filgrastim dosage was adjusted to a level that maintained a median monthly ANC between 1,500 cells/mm3 and 10,000 cells/mm3. The dosage was increased if the median ANC was below 1,500 cells/mm3 for 2 weeks. The dosage was decreased if the median ANC was 10,000 cells/mm3 or more for 4 weeks. The median ANC was significantly improved in 62 patients who received 4 months of filgrastim compared with 60 patients who received 4 months of observation only (6.1 cells/mm3 vs. 0.21 cells/mm3; p-value 0.001 or less). In patients with congenital neutropenia, the median ANC was 3.45 cells/mm3 in the filgrastim arm (n = 31; median age of 7.7 years; range, 1.1 to 32.9 years) and 0.15 cells/mm3 in the observation only arm (n = 29; median age of 8 years; range, 0.6 to 33.8 years).

5 mcg/kg subcutaneously once daily initially. Individualize the dosage to maintain clinical benefit based on patient clinical course and absolute neutrophil count (ANC). In a postmarketing surveillance study in 731 patients (adults, n = 302; pediatric patients, n = 429), the median filgrastim dose was 2.1 mcg/kg/day in patients with cyclic neutropenia.   The starting dose for cyclic neutropenia 5.75 mcg/kg/day (based on actual body weight) given subcutaneously in a randomized trial in patients with chronic severe neutropenia (n = 123; median age of 12.1 years; range, 7 months to 76 years). In this study, the filgrastim dosage was adjusted to a level that maintained a median monthly ANC between 1,500 cells/mm3 and 10,000 cells/mm3. The dosage was increased if the median ANC was below 1,500 cells/mm3 for 2 weeks. The dosage was decreased if the median ANC was 10,000 cells/mm3 or more for 4 weeks The median ANC was significantly improved in 62 patients who received 4 months of filgrastim compared with 60 patients who received 4 months of observation only (6.1 cells/mm3 vs. 0.21 cells/mm3; p-value 0.001 or less). In patients with cyclic neutropenia, the median ANC was 9.88 cells/mm3 in the filgrastim arm (n = 10; median age of 10.7 years; range, 2.5 to 47.2 years) and 0.67 cells/mm3 in the observation only arm (n = 11; median age of 27.4 years; range, 10.5 to 59.1 years).

5 mcg/kg subcutaneously once daily initially. Individualize the dosage to maintain clinical benefit based on patient clinical courses and absolute neutrophil count (ANC). In a postmarketing surveillance study in 731 patients (adults, n = 302; pediatric patients, n = 429), the median filgrastim dose was 1.2 mcg/kg/day in patients with idiopathic neutropenia. The starting dose for idiopathic neutropenia was 3.45 mcg/kg/day (based on actual body weight) given subcutaneously in a randomized trial in patients with chronic severe neutropenia (n = 123). In this study, the filgrastim dosage was adjusted to a level that maintained a median monthly ANC between 1,500 cells/mm3 and 10,000 cells/mm3. The dosage was increased if the median ANC was below 1,500 cells/mm3 for 2 weeks. The dosage was decreased if the median ANC was 10,000 cells/mm3 or more for 4 weeks The median ANC was significantly improved in 62 patients who received 4 months of filgrastim compared with 60 patients who received 4 months of observation only (6.1 cells/mm3 vs. 0.21 cells/mm3; p-value 0.001 or less). In patients with idiopathic neutropenia, the median ANC was 9.72 cells/mm3 in the filgrastim arm (n = 21; median age of 28.5 years; range, 2.1 to 69.1 years) and 0.23 cells/mm3 in the observation only arm (n = 20; median age of 30.8 years; range, 1.3 to 75.7 years).

5 mcg/kg/day administered as a subcutaneous injection. Based on the duration and severity of the absolute neutrophil count (ANC) nadir, the filgrastim dose may be escalated in increments of 5 mcg/kg for each cycle of chemotherapy. Discontinue filgrastim if the ANC is increased to more than 10,000 cells/mm3.   Consider rounding the dose to the nearest vial size. Treatment with filgrastim should be started between 24 and 72 hours after chemotherapy and continued until the ANC is at least 2,000 to 3,000 cells/mm3. The American Society of Clinical Oncology clinical guidelines recommend the use of colony-stimulating factors (CSFs) for primary prophylaxis in patients who are at high-risk of developing febrile neutropenia (e.g., age more than 65 years, prior episodes of febrile neutropenia, poor nutritional status, poor performance status, open wounds or active infections, combined chemoradiotherapy, history of extensive treatment including large radiation ports, tumor bone marrow involvement resulting in cytopenias, and advanced cancer), have other comorbidities, or who are receiving dose-dense chemotherapy with the intention of cure or a chemotherapy regimen with an expected incidence of febrile neutropenia of 20% or more.

5 mcg/kg/day administered as a subcutaneous injection. Based on the duration and severity of the absolute neutrophil count (ANC) nadir, the filgrastim dose may be escalated in increments of 5 mcg/kg for each cycle of chemotherapy. Discontinue filgrastim if the ANC is increased to more than 10,000 cells/mm3.   Treatment with filgrastim should be started between 24 and 72 hours after chemotherapy and continued until the ANC is at least 2,000 to 3,000 cells/mm3. The American Society of Clinical Oncology clinical guidelines recognize that the use of colony-stimulating factors are guided by clinical protocols. Filgrastim may be considered as primary prophylaxis in children who are at high-risk for febrile neutropenia.

5 mcg/kg/day administered as an IV infusion over 15 to 30 minutes or by continuous IV infusion. Based on the duration and severity of the absolute neutrophil count (ANC) nadir, the filgrastim dose may be escalated in increments of 5 mcg/kg for each cycle of chemotherapy. Discontinue filgrastim if the ANC is increased to more than 10,000 cells/mm3.   Consider rounding the dose to the nearest vial size. Treatment with filgrastim should be started between 24 and 72 hours after chemotherapy and continued until the ANC is at least 2,000 to 3,000 cells/mm3. The American Society of Clinical Oncology clinical guidelines recommend the use of colony-stimulating factors (CSFs) for primary prophylaxis in patients who are at high-risk of developing febrile neutropenia (e.g., age more than 65 years, prior episodes of febrile neutropenia, poor nutritional status, poor performance status, open wounds or active infections, combined chemoradiotherapy, history of extensive treatment including large radiation ports, tumor bone marrow involvement resulting in cytopenias, and advanced cancer), have other comorbidities, or who are receiving dose-dense chemotherapy with the intention of cure or a chemotherapy regimen with an expected incidence of febrile neutropenia of 20% or more.

5 mcg/kg/day administered as an IV infusion over 15 to 30 minutes or by continuous IV infusion. Based on the duration and severity of the absolute neutrophil count (ANC) nadir, the filgrastim dose may be escalated in increments of 5 mcg/kg for each cycle of chemotherapy. Discontinue filgrastim if the ANC is increased to more than 10,000 cells/mm3.   Treatment with filgrastim should be started between 24 and 72 hours after chemotherapy and continued until the ANC is at least 2,000 to 3,000 cells/mm3. The American Society of Clinical Oncology clinical guidelines recognize that the use of colony-stimulating factors are guided by clinical protocols. Filgrastim may be considered as primary prophylaxis in children who are at high-risk for febrile neutropenia.

5 mcg/kg/day administered as a subcutaneous injection. Based on the duration and severity of the absolute neutrophil count (ANC) nadir, the filgrastim dose may be escalated in increments of 5 mcg/kg for each cycle of chemotherapy. Discontinue filgrastim if the ANC is increased to more than 10,000 cells/mm3.   Consider rounding the dose to the nearest vial size . Treatment with filgrastim should be started between 24 and 72 hours after chemotherapy and continued until the ANC is at least 2,000 to 3,000 cells/mm3. The American Society of Clinical Oncology (ASCO) clinical guidelines suggest that colony-stimulating factors (CSFs) may be used after initial induction therapy; acute myelogenous leukemia (AML) patients aged more than 55 years may benefit the most from post-induction CSF therapy. The benefit of shortening the duration of neutropenia has been demonstrated with post-consolidation CSF use in AML patients in remission; therefore, the ASCO guidelines recommend the use of CSFs in this setting.

5 mcg/kg/day administered as a subcutaneous injection. Based on the duration and severity of the absolute neutrophil count (ANC) nadir, the filgrastim dose may be escalated in increments of 5 mcg/kg for each cycle of chemotherapy. Discontinue filgrastim if the ANC is increased to more than 10,000 cells/mm3.   Treatment with filgrastim should be started between 24 and 72 hours after chemotherapy and continued until the ANC is at least 2,000 to 3,000 cells/mm3. The American Society of Clinical Oncology (ASCO) clinical guidelines suggest that colony-stimulating factors (CSFs) may be used after initial acute myelogenous leukemia (AML) induction therapy. The benefit of shortening the duration of neutropenia has been demonstrated with post-consolidation CSF use in AML patients in remission; therefore, the ASCO guidelines recommend the use of CSFs in this setting.

5 mcg/kg/day administered as an IV infusion over 15 to 30 minutes or by continuous IV infusion. Based on the duration and severity of the absolute neutrophil count (ANC) nadir, the filgrastim dose may be escalated in increments of 5 mcg/kg for each cycle of chemotherapy. Discontinue filgrastim if the ANC is increased to more than 10,000 cells/mm3.   Consider rounding the dose to the nearest vial size . Treatment with filgrastim should be started between 24 and 72 hours after chemotherapy and continued until the ANC is at least 2,000 to 3,000 cells/mm3. The American Society of Clinical Oncology (ASCO) clinical guidelines suggest that colony-stimulating factors (CSFs) may be used after initial induction therapy; acute myelogenous leukemia (AML) patients aged more than 55 years may benefit the most from post-induction CSF therapy. The benefit of shortening the duration of neutropenia has been demonstrated with post-consolidation CSF use in AML patients in remission; therefore, the ASCO guidelines recommend the use of CSFs in this setting.

5 mcg/kg/day administered as an IV infusion over 15 to 30 minutes or by continuous IV infusion. Based on the duration and severity of the absolute neutrophil count (ANC) nadir, the filgrastim dose may be escalated in increments of 5 mcg/kg for each cycle of chemotherapy. Discontinue filgrastim if the ANC is increased to more than 10,000 cells/mm3.   Treatment with filgrastim should be started between 24 and 72 hours after chemotherapy and continued until the ANC is at least 2,000 to 3,000 cells/mm3. The American Society of Clinical Oncology (ASCO) clinical guidelines suggest that colony-stimulating factors (CSFs) may be used after initial acute myelogenous leukemia (AML) induction therapy. The benefit of shortening the duration of neutropenia has been demonstrated with post-consolidation CSF use in AML patients in remission; therefore, the ASCO guidelines recommend the use of CSFs in this setting.

5 mcg/kg IV or subcutaneously once daily, rounded to the nearest vial size. Begin 24 to 72 hours after completion of chemotherapy. Administration of filgrastim may shorten the duration of neutropenia (ANC less than 1,000/mm3) by approximately 1 week. Filgrastim may be given along with corticosteroid/antimetabolite therapy; concurrent therapy does not appear to prolong the myelosuppressive effect of the chemotherapy.

5 mcg/kg/day administered as a subcutaneous injection. Based on the duration and severity of the absolute neutrophil count (ANC) nadir, the filgrastim dose may be escalated in increments of 5 mcg/kg for each cycle of chemotherapy. Discontinue filgrastim if the ANC is increased to more than 10,000 cells/mm3.   Consider rounding the dose to the nearest vial size. Treatment with filgrastim should be started between 24 and 72 hours after chemotherapy and continued until the ANC is at least 2,000 to 3,000 cells/mm3. The American Society of Clinical Oncology clinical guidelines recommend the use of colony-stimulating factors (CSFs) for secondary prophylaxis in patients who had a neutropenic complication after a prior cycle of chemotherapy (when a CSF was not given as primary prophylaxis) and in situations that a chemotherapy dose reduction may compromise the disease-free or overall survival or treatment outcome.

5 mcg/kg/day administered as a subcutaneous injection. Based on the duration and severity of the absolute neutrophil count (ANC) nadir, the filgrastim dose may be escalated in increments of 5 mcg/kg for each cycle of chemotherapy. Discontinue filgrastim if the ANC is increased to more than 10,000 cells/mm3.   Treatment with filgrastim should be started between 24 and 72 hours after chemotherapy and continued until the ANC is at least 2,000 to 3,000 cells/mm3. The American Society of Clinical Oncology clinical guidelines recognize that use of colony-stimulating factors is guided by clinical protocols. Filgrastim may be considered as secondary prophylaxis in children who are at high-risk for febrile neutropenia.

5 mcg/kg/day administered as an IV infusion over 15 to 30 minutes or by continuous IV infusion. Based on the duration and severity of the absolute neutrophil count (ANC) nadir, the filgrastim dose may be escalated in increments of 5 mcg/kg for each cycle of chemotherapy. Discontinue filgrastim if the ANC is increased to more than 10,000 cells/mm3.   Consider rounding the dose to the nearest vial size. Treatment with filgrastim should be started between 24 and 72 hours after chemotherapy and continued until the ANC is at least 2,000 to 3,000 cells/mm3. The American Society of Clinical Oncology clinical guidelines recommend the use of colony-stimulating factors (CSFs) for secondary prophylaxis in patients who had a neutropenic complication after a prior cycle of chemotherapy (when a CSF was not given as primary prophylaxis) and in situations that a chemotherapy dose reduction may compromise the disease-free or overall survival or treatment outcome.

5 mcg/kg/day administered as an IV infusion over 15 to 30 minutes or by continuous IV infusion. Based on the duration and severity of the absolute neutrophil count (ANC) nadir, the filgrastim dose may be escalated in increments of 5 mcg/kg for each cycle of chemotherapy. Discontinue filgrastim if the ANC is increased to more than 10,000 cells/mm3.   Treatment with filgrastim should be started between 24 and 72 hours after chemotherapy and continued until the ANC is at least 2,000 to 3,000 cells/mm3. The American Society of Clinical Oncology clinical guidelines recognize that use of colony-stimulating factors is guided by clinical protocols. Filgrastim may be considered as secondary prophylaxis in children who are at high-risk for febrile neutropenia.

10 mcg/kg/day administered as an IV infusion; infuse over no longer than 24 hours. Start no sooner than 24 hours after chemotherapy and 24 hours after bone marrow infusion. Titrate the daily dose according to the absolute neutrophil count (ANC). When the ANC is above 1,000 cells/mm3 for 3 consecutive days, reduce to 5 mcg/kg/day. After this dose reduction, discontinue filgrastim when the ANC remains above 1,000 cells/mm3 for 3 consecutive days; resume therapy at 5 mcg/kg/day if the ANC decreases to less than 1,000 cells/mm3 after drug discontinuation. If the ANC is less than 1,000 cells/mm3 when a patient is receiving 5 mcg/kg/day, increase filgrastim dose to 10 mcg/kg/day. The American Society of Clinical Oncology clinical guidelines recommend colony-stimulating factors following an autologous peripheral blood stem-cell transplant.

10 mcg/kg/day administered as a subcutaneous injection. Start at least 4 days before the first leukapheresis procedure and continue until the last leukapheresis procedure. Although the optimal duration of administration and leukapheresis schedule have not been determined, a safe and effective schedule involved administration of filgrastim for 6 to 7 days, with leukapheresis on days 5, 6, and 7. Discontinue filgrastim if the white blood cell count is more than 100,000 cells/mm3.

10 mcg/kg/day as a subcutaneous injection. Start filgrastim therapy as soon as possible after a patient received or is suspected of receiving a radiation dose greater than 2 gray (Gy). Use information from public health authorities, biodosimetry (if available), or clinical findings (e.g., time to onset of vomiting or lymphocyte depletion kinetics) to estimate a patient’s level of radiation exposure. Obtain a complete blood cell count panel prior to starting filgrastim (if access to laboratory testing is readily available) and then every 3 days during filgrastim therapy. Discontinue therapy when the absolute neutrophil count (ANC) is greater than 1,000 cells/mm3 for 3 consecutive days or the ANC is greater than 10,000 cells/mm3 after a radiation-induced nadir. Advise patients that efficacy for this indication was based on animal data in monkeys. For ethical reasons, filgrastim could not be studied in human subjects with acute radiation exposure. The 60-day mortality rate was significantly decreased in non-human primates who received filgrastim compared with placebo (21% vs. 59%; p = 0.023) starting 1 day (24 hours) after acute myelosuppressive radiation exposure in a randomized, blinded, placebo-controlled study; this study was halted at an interim analysis. For ethical reasons, filgrastim could not be studied in human subjects with acute radiation exposure. ANIMAL STUDY: Filgrastim 10 mcg/kg subcutaneously once daily (n = 24) or placebo (n = 22) was administered in rhesus macaques exposed to total body irradiation (TBI) of 7.4 +/- 0.15 Gy delivered at 0.8 +/- 0.03 Gy/minute. The TBI represented a dose that would be lethal in 50% of animals by 60 days of follow-up (LD 50/60). Treatment was stopped when the ANC was at least 1,000 cells/mm3 for 3 consecutive days, the ANC was at least 10,000 cells/mm3 for more than 2 consecutive days within study days 1 to 5, or the ANC was at least 10,000 cells/mm3 any time after study day 5. All animal subjects received supportive care including IV fluids, antibiotics, and blood transfusions. The timing of filgrastim administration appears important. The 60-day mortality rate was not significantly decreased in rhesus macaques who received filgrastim vs. placebo starting 48 hours after exposure to TBI at approximately the LD 50/60 in a randomized, blinded, placebo-controlled study (n = 80); this study was stopped for futility at an interim analysis.

10 mcg/kg/day as a subcutaneous injection. Start filgrastim therapy as soon as possible after a patient received or is suspected of receiving a radiation dose greater than 2 gray (Gy). Use information from public health authorities, biodosimetry (if available), or clinical findings (e.g., time to onset of vomiting or lymphocyte depletion kinetics) to estimate a patient’s level of radiation exposure. Obtain a complete blood cell count panel prior to starting filgrastim (if access to laboratory testing is readily available) and then every 3 days during filgrastim therapy. Discontinue therapy when the absolute neutrophil count (ANC) is greater than 1,000 cells/mm3 for 3 consecutive days or the ANC is greater than 10,000 cells/mm3 after a radiation-induced nadir. Advise patients that efficacy for this indication was based on animal data in monkeys. The 60-day mortality rate was significantly decreased in non-human primates who received filgrastim compared with placebo (21% vs. 59%; p = 0.023) starting 1 day (24 hours) after acute myelosuppressive radiation exposure in a randomized, blinded, placebo-controlled study; this study was halted at an interim analysis. For ethical reasons, filgrastim could not be studied in human subjects with acute radiation exposure. ANIMAL STUDY: Filgrastim 10 mcg/kg subcutaneously once daily (n = 24) or placebo (n = 22) was administered in rhesus macaques exposed to total body irradiation (TBI) of 7.4 +/- 0.15 Gy delivered at 0.8 +/- 0.03 Gy/minute. The TBI represented a dose that would be lethal in 50% of animals by 60 days of follow-up (LD 50/60). Treatment was stopped when the ANC was at least 1,000 cells/mm3 for 3 consecutive days, the ANC was at least 10,000 cells/mm3 for more than 2 consecutive days within study days 1 to 5, or the ANC was at least 10,000 cells/mm3 any time after study day 5. All animal subjects received supportive care including IV fluids, antibiotics, and blood transfusions. The timing of filgrastim administration appears important. The 60-day mortality rate was not significantly decreased in rhesus macaques who received filgrastim vs. placebo starting 48 hours after exposure to TBI at approximately the LD 50/60 in a randomized, blinded, placebo-controlled study (n = 80); this study was stopped for futility at an interim analysis.

5 mcg/kg/day IV or subcutaneously, rounded to the nearest vial size. Data supporting the routine, long-term use of filgrastim for MDS are lacking. Sometimes used along with erythropoesis stimulation to help induce hemoglobin response and transfusion independence. Guidelines suggest consideration for neutropenic MDS patients with recurrent infections, although there a few data from clinical trials proving infection prevention benefit.

5 to 10 mcg/kg/day (300 to 600 mcg/day) 1 to 3 times weekly have been given. Guidelines state that ganciclovir-related neutropenia can often be reversed with granulocyte colony stimulating factor (G-CSF); however, studies evaluating use of G-CSF in persons with HIV to reduce the risk of serious bacterial infection have failed to demonstrate benefit.

The usual off-label dose protocol is 5 mcg/kg subcutaneously once daily, beginning at day 8 of immunosuppressants, and continued until day 240 unless complete remission occurs earlier. Used as an adjunct to immunosuppressants (e.g., antithymocyte globulin, cyclosporine, corticosteroids) in first-line protocols for severe aplastic anemia (SAA). The addition of G-CSF reduces the rate of early infection episodes and days of hospitalization and appears to help identify non-responders to standard treatment, but has no effect on overall survival, event-free survival, remission, relapse rates, or mortality. In a post hoc analysis of patients receiving G-CSF, the lack of a neutrophil response by day 30 was associated with significantly lower response rate (56% vs. 81%; p = 0.048) and survival (65% vs. 87%; p = 0.031). Randomized clinical trials have not supported an association of G-CSF use with secondary malignancies, though earlier retrospective data suggested an association.

The usual initial off-label dose is 5 mcg/kg subcutaneously once daily; doses exceeding 10 mcg/kg/day have been reported in children. Used as an adjunct to immunosuppressants for pediatric patients with severe aplastic anemia (SAA) who have severe neutropenia. However, bone marrow transplant is usually therapy of choice.

†Indicates off-label use

No dosage adjustment is necessary.

No dosage adjustment is necessary.

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.

Filgrastim (E. coli)/Neupogen/Nivestym/Releuko/Zarxio Intravenous Inj Sol: 0.5mL, 0.8mL, 1mL, 1.6mL, 300mcg, 480mcg
Filgrastim (E. coli)/Neupogen/Nivestym/Releuko/Zarxio Subcutaneous Inj Sol: 0.5mL, 0.8mL, 1mL, 1.6mL, 300mcg, 480mcg

NOTE: Maximum daily dosage is indication dependent.

30 mcg/kg/day IV. Subcutaneous, 24 mcg/kg/day (rarely, 100 mcg/kg/day subcutaneously or higher in patients with severe congenital neutropenia).

30 mcg/kg/day IV. Subcutaneous, 24 mcg/kg/day (rarely, 100 mcg/kg/day subcutaneously or higher in patients with severe congenital neutropenia).

Subcutaneous, 15 mcg/kg/day (rarely, 100 mcg/kg/day or higher in patients with severe congenital neutropenia).

Subcutaneous, 15 mcg/kg/day (rarely, 100 mcg/kg/day or higher in patients with severe congenital neutropenia).

7 to 11 months: Subcutaneous, 12 mcg/kg/day (rarely, 100 mcg/kg/day or higher in patients with severe congenital neutropenia).

Granulocyte colony-stimulating factor (G-CSF) is a glycoprotein involved in the regulation and production of neutrophils in response to host defense needs. Filgrastim 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. Exogenous G-CSF increases the number of circulating hematopoietic progenitor cells in a dose-dependent manner. Hematopoietic stem and progenitor cell mobilization is thought to be related to the ability of G-CSF to downregulate endothelial intercellular adhesion molecule 1 (ICAM-1), and upregulate vascular cell adhesion molecule-1.

Filgrastim is administered intravenously (IV) or subcutaneously. Pharmacokinetic data are similar in healthy subjects and cancer patients. The volume of distribution averaged 150 mL/kg. Clearance is nonlinear and is dependent on drug concentration and neutrophil count. G-CSF receptor-mediated clearance is saturated by a high concentration of filgrastim and clearance is diminished by neutropenia. Filgrastim is cleared by the kidney. The elimination half-life is approximately 3.5 hours, and the clearance is about 0.5 to 0.7 mL/minute/kg following IV filgrastim administration. The half-life of filgrastim is similar following IV (231 minutes) or subcutaneous (210 minutes) administration. Additionally, single IV doses or daily IV doses resulted in comparable half-life values.
A dose-dependent increase in circulating neutrophil counts occurred following filgrastim administration (dose range, 1 to 70 mcg/kg/day) in patients with nonmyeloid malignancies. This dose-dependent neutrophil increase occurred with IV (1 to 70 mcg/kg twice daily), subcutaneous (1 to 3 mcg/kg once daily), or continuous subcutaneous infusion (3 to 11 mcg/kg/day) administration. In most cases, the neutrophil count returned to baseline within 4 days of stopping filgrastim.
Affected cytochrome P450 isoenzymes and drug transporters: None

The steady-state concentration was achieved and there was no evidence of drug accumulation when filgrastim 20 mcg/kg/day was given as a continuous 24-hour IV infusion over 11 to 20 days.

The absolute bioavailability of filgrastim is 60% to 70% following subcutaneous administration. The peak concentration (Cmax) was 4 and 49 nanograms/mL following subcutaneous filgrastim doses of 3.45 mcg/kg and 11.5 mcg/kg, respectively. The time to peak concentration (Tmax) ranged from 2 to 8 hours.

The potential risk to the fetus with the use of filgrastim during pregnancy is unknown; there are no adequate and well-controlled clinical studies in pregnant women. Several observational studies have shown no major differences in pregnancy outcome (including miscarriage and preterm labor), neonatal complications (including birth weight), and infections between treated and untreated women. No malformations were observed during animal studies. Reduced embryo-fetal survival and increased fetal abortion were observed in pregnant rabbits who received filgrastim doses that were 2- to 10-times higher than doses used in humans.

The transfer of filgrastim into human milk has been documented in published literature. However, no adverse effects in breast-feeding infants have been noted. The effects of filgrastim on human milk production are unknown. Other recombinant filgrastim products are poorly secreted into breast milk, and filgrastim is not orally absorbed by neonates. Consider the benefits of breast-feeding compared with the risk of a potential adverse event in the infant prior to administering filgrastim in a lactating woman.