filgrastim (G-CSF, Neupogen, tbo-filgrastim, Granix, Zarxio, filgrastim-sndz)
Classes: Hematopoietic Growth Factors
Dosing and uses of Neupogen, Granix (filgrastim, tbo-filgrastim, G-CSF)
Adult dosage forms and strengths
injectable solution (Neupogen)
- 300mcg/mL
- 480mcg/1.6mL
prefilled syringe for SC injection (Neupogen, tbo-filgrastim [Granix], filgrastim-sndz [Zarxio])
- 300mcg/0.5mL
- 480mcg/0.8mL
Biosimilars to Neupogen
- Zarxio
Myelosuppressive Chemotherapy Treatment
Neupogen, Granix, Zarxio
Indicated to decrease infection incidence‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a significant incidence of severe neutropenia with fever
5 mcg/kg SC/IV qDay initially, may increase by 5 mcg/kg according to duration and severity of ANC
Do not administer within the 24-hr period prior to chemotherapy
A transient increase in neutrophil count is typically seen 1 to 2 days after initiation; therefore, to ensure a sustained therapeutic response‚ administer daily for up to 2 weeks or until the ANC has reached 10‚000/mm³ following the expected chemotherapy-induced neutrophil nadir
Duration of therapy needed to attenuate chemotherapy-induced neutropenia may be dependent on the myelosuppressive potential of the chemotherapy regimen employed
Induction or Consolidation Chemotherapy
Neupogen, Zarxio
Indicated for reducing the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia
5 mcg/kg SC/IV qDay intially, may increase by 5 mcg/kg for each chemotherapy cycle according to duration and severity of ANC
Do not administer within the 24-hr period prior to chemotherapy
A transient increase in neutrophil count is typically seen 1 to 2 days after initiation; therefore, to ensure a sustained therapeutic response‚ administer daily for up to 2 weeks or until the ANC has reached 10‚000/mm³ following the expected chemotherapy-induced neutrophil nadir
Duration of therapy needed to attenuate chemotherapy-induced neutropenia may be dependent on the myelosuppressive potential of the chemotherapy regimen employed
Bone Marrow Transplantation
Neupogen, Zarxio
Indicated to reduce the duration of neutropenia and neutropenia-related clinical sequelae (eg‚ febrile neutropenia) in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation
Following bone marrow transplantation (BMT): 10 mcg/kg/day IV infusion over 4-24 hr (do not exceed 24 hr infusion)
Administer the first dose at least 24 hr after cytotoxic chemotherapy and at least 24 hr after bone marrow infusion
Monitor CBCs and platelet counts frequently following marrow transplantation
Dose titration
- During the period of neutrophil recovery‚ titrate the daily dosage against the neutrophil response
- ANC >1000/mm³: Reduce dose to 5 mcg/kg/day, THEN
- If ANC remains >1000/mm³ for 3 more consecutive days: Discontinue filgrastim, THEN
- If ANC decreases to <1000³: Resume at 5 mcg/kg/day
Peripheral Blood Progenitor Cell Collection
Neupogen, Zarxio
Indicated for the mobilization of autologous peripheral blood progenitor cells (PBPC) into the peripheral blood for collection by leukapheresis
10 mcg/kg/day SC
Initiate at least 4 days before first leukapheresis; continue until last day of leukapheresis
Optimal duration of administration and leukapheresis schedule have not been established‚ administration for 6 to 7 days with leukaphereses on days 5‚ 6‚ and 7 was found to be safe and effective in clinical studies described in prescribing information
Monitor neutrophil counts after 4 days‚ and discontinue if the WBC count rises to >100‚000/mm³
Severe Chronic Neutropenia
Neupogen, Zarxio
Indicated for chronic administration to reduce the incidence and duration of sequelae of neutropenia (eg‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with severe chronic neutropenia (SCN) including congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia
Congenital: Initial 6 mcg/kg SC q12hr
Idiopathic/cyclic: Initial 5 mcg/kg/day SC
Dosage modifications (SCN)
- Chronic daily administration is required to maintain clinical benefit
- Individualize dose based on the clinical course as well as ANC
- Postmarket analysis showed median daily doses of 6 mcg/kg (congenital neutropenia), 2.1 mcg/kg (cyclic neutropenia), and 1.2 mcg/kg (idiopathic neutropenia)
- In rare instances, patients with congenital neutropenia have required doses ≥100 mcg/kg/day
Monitoring (SCN)
- Monitor CBC count (with differential and platelet counts) during the initial 4 weeks and during the 2 weeks following any dosage adjustment
- Once a patient is clinically stable‚ monitor monthly during the first year of treatment
- Thereafter, if the patient is clinically stable, less frequent routine monitoring is recommended
Acute Exposure to Myelosuppressive Radiation Doses
Neupogen
Indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation (hematopoietic syndrome of acute radiation syndrome)
10 mcg/kg SC as a single daily injection for patients exposed to myelosuppressive doses of radiation
Administer as soon as possible after suspected or confirmed exposure to radiation doses >2 gray (Gy)
Estimate a patient’s absorbed radiation dose based on information from public health authorities, biodosimetry if available, or clinical findings (eg, time to onset of vomiting, lymphocyte depletion kinetics)
Obtain baseline CBC and then serial CBCs ~q3days until the ANC remains >1,000/mm³ for 3 consecutive CBCs
Do not delay administration if a CBC is not readily available
Continue administration until the ANC remains >1,000/mm³ for 3 consecutive CBCs or is >10,000/mm³ after a radiation-induced nadir
Orphan Designations
Ganciclovir-related neutropenia: Treatment of patients with AIDS who, in addition, are afflicted with cytomegalovirus retinitis and are being treated with ganciclovir
Treatment of amyotropic lateral sclerosis (ALS)
Sponsors
- Amgen, Inc; One Amgen Center Dr; Thousand Oaks, CA 91320-1799
- Neurovision Pharma GmbH; Emil-Geis Str. 4; Grunwald82031, Germany
Administration
SC bolus injection
- SC injection may be administered by healthcare professional, caregiver, or patient
- Sites for SC injections include the abdomen (except for the 2-inch area around the navel), the front of the middle thighs, the upper outer areas of the buttocks, or the upper back portion of the upper arms
- Rotate injection site daily
- Do not inject into an area that is tender, red, bruised or hard, or that has scars or stretch marks
Pediatric dosage forms and strengths
injectable solution (Neupogen)
- 300mcg/mL
- 480mcg/1.6mL
prefilled syringe for SC injection (Neupogen, tbo-filgrastim [Granix])
- 300mcg/0.5mL
- 480mcg/0.8mL
Peripheral Blood Progenitor Cell Collection
As adults; 10 mcg/kg/day SC
Initiate 4 days before leukapheresis; continue until last day of leukapheresis
Myelosuppressive Chemotherapy Treatment (Off-label)
5-10 mcg/kg qDay IV/SC for14 days
Give daily until ANC >10,000/mm³
Congenital Neutropenia or Agranulocytosis (Off-label)
As adults; Initial 6 mcg/kg SC q12hr
Dosage range: 3-15 mcg/kg/day SC qDay or divided q12hr
Administration
SC bolus injection
- SC injection may be administered by healthcare professional, caregiver, or patient
- Sites for SC injections include the abdomen (except for the 2-inch area around the navel), the front of the middle thighs, the upper outer areas of the buttocks, or the upper back portion of the upper arms
- Rotate injection site daily
- Do not inject into an area that is tender, red, bruised or hard, or that has scars or stretch marks
Neupogen, Granix (filgrastim, tbo-filgrastim, G-CSF) adverse (side) effects
>10%
Nausea (57%)
Vomiting (57%)
Bone pain (22%-33%)
Alopecia (18%)
Diarrhea (14%)
Fever (12%)
Fatigue (11%)
1-10%
Headache
Anorexia
Chest pain
Cough
Dyspnea
Constipation
Stomatitis
Sore throat
Rash
Frequency not defined
Elevated uric acid
Elevated lactate dehydrogenase
Elevated alkaline phosphatase
Postmarketing Reports
Splenic rupture
ARDs
Glomerulonephritis
Alveolar hemorrhage and hemoptysis
Sickle cell crisis
Cutaneous vasculitis
Sweet’s syndrome (acute febrile neutrophilic dermatosis)
Decreased bone density and osteoporosis in children with severe chronic neutropenia receiving chronic treatment
Warnings
Contraindications
Hypersensitivity to E. coli derived proteins
Cautions
Allergic reactions reported (angioneurotic edema, dermatitis allergic, hypersensitivity, rash, pruritic rash and urticaria)
Associated with rare cases of potentially fatal splenic rupture; evaluate if patient experiences left upper abdominal and/or shoulder tip pain
Rare cases of acute respiratory distress syndrome reported
Monitor for thrombocytopenia
Sickle cell crisis: Severe and sometimes fatal crisis can occur; discontinue drug if suspected
Glomerulonephritis reported; if suspected, evaluate for cause; if causality likely, consider dose-reduction or interruption
Off-label use for PBPC mobilization has resulted in alveolar hemorrhage, resulting in pulmonary infiltrates and hemoptysis
Pregnancy and lactation
Pregnancy category: C
Women who become pregnant during treatment are encouraged to enroll in Amgen's Pregnancy Surveillance Program; call 1-800-77-AMGEN (1-800-772-6436) to enrolL
Lactation: excretion in milk unknown; use with caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Neupogen, Granix (filgrastim, tbo-filgrastim, G-CSF)
Mechanism of action
Recombinant human G-CSF, acts on hematopoietic cells to stimulate production, maturation and activation of neutrophils; increases migration and cytotoxicity of neutrophils.
Absorption
100% (SC)
Peak Plasma Time: 2-8 hr
Distribution
Vd: 0.15 L/kg
Metabolism
Degraded systemically
Elimination
Duration: Neutrophil counts decrease to baseline in approximately 4 days
Half-life elimination: 1.8-3.5 hr
Clearance: 0.5-0.7 mL/min/kg
Administration
IV Incompatibilities
Y-site: amphotericin B, cefepime, cefoperazone, cefotaxime, cefoxitin, ceftizoxime, ceftriaxone, cefuroxime, clindamycin, dactinomycin, etoposide, fluorouracil, furosemide, heparin, mannitol, methylprednisolone sodium succinate, metronidazole, mitomycin, piperacillin, prochlorperazine, thiotepa
IV Compatibilities
Y-site (partial list): acyclovir, ampicillin, bleomycin, carboplatin, carmustine, cyclophosphamide, diphenhydramine, daunorubicin,. doxorubicin, fluconazole, metoclopramide, morphine SO4, KCl, Na-bicarB
IV Preparation
Vials may be diluted in D5W to >15 mcg/mL for infusion
5-15 mcg/mL dilution: Protect from adsorption to plastic materials by the addition of human albumin to a final concentration of 2 mg/mL
Do not dilute with saline at any time, because the product may precipitate
IV Administration
Short IV infusion over 15-30 min, Or
Continuous IV infusion
SC Administration
Administer undiluted by SC in the outer area of upper arms, abdomen, thighs, or upper outer areas of the buttock
Storage
Clear, colorless solution
Store refrigerated and protect from light
Diluted solution: Can be stored at room temperature for up to 24 hr (includes infusion time)
Do not shake