Dosage guidance:
Dosing: May round the dose to the nearest vial size for convenience and cost minimization for oncology indications (Ref). International considerations: Dosages below expressed as micrograms; 1 mcg = 100,000 units (Ref).
Dosage form information: Nivestym (filgrastim-aafi), Releuko (filgrastim-ayow), and Zarxio (filgrastim-sndz) are approved as biosimilars to Neupogen (filgrastim). In Canada, Grastofil is a biosimilar to Neupogen (filgrastim).
Acute myeloid leukemia following induction or consolidation chemotherapy (Neupogen and filgrastim biosimilars): Note: Do not administer filgrastim in the period 24 hours before to 24 hours after administration of cytotoxic chemotherapy because of the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy.
SUBQ, IV: 5 mcg/kg/day; doses may be increased by 5 mcg/kg (for each chemotherapy cycle) according to the duration and severity of the neutropenia; continue for up to 14 days until the ANC reaches 10,000/mm3. Discontinue if the ANC surpasses 10,000/mm3 after the expected chemotherapy-induced neutrophil nadir.
Alcoholic hepatitis, severe (off-label use): SUBQ : 5 mcg/kg every 12 hours for 5 consecutive days in combination with standard medical therapy (pentoxifylline and nutritional therapy) and supportive care (Ref).
Bone marrow transplantation (Neupogen and filgrastim biosimilars): IV infusion: 10 mcg/kg/day (administer ≥24 hours after chemotherapy and ≥24 hours after bone marrow infusion); adjust the dose according to the duration and severity of neutropenia; recommended steps based on neutrophil response:
When ANC >1,000/mm3 for 3 consecutive days: Reduce dose to 5 mcg/kg/day.
If ANC remains >1,000/mm3 for 3 more consecutive days: Discontinue.
If ANC decreases to <1,000/mm3: Resume at 5 mcg/kg/day.
If ANC decreases to <1,000/mm3 during the 5 mcg/kg/day dose: Increase dose to 10 mcg/kg/day and follow the above steps.
Chemotherapy-induced myelosuppression in nonmyeloid malignancies:
Note: Do not administer filgrastim in the period 24 hours before to 24 hours after administration of cytotoxic chemotherapy because of the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy. WBC growth factors are generally recommended to reduce the risk of neutropenic fever when the anticipated risk of neutropenic fever for a chemotherapy regimen is approximately ≥20% (Ref).
Neupogen and filgrastim biosimilars: SUBQ, IV: 5 mcg/kg/day; doses may be increased by 5 mcg/kg (for each chemotherapy cycle) according to the duration and severity of the neutropenia; continue for up to 14 days until the absolute neutrophil count (ANC) reaches 10,000/mm3. Discontinue when ANC >10,000/mm3 after the expected chemotherapy-induced neutrophil nadir (to avoid potential excessive leukocytosis).
Tbo-filgrastim: SUBQ: 5 mcg/kg/day; continue until anticipated nadir has passed and neutrophil count has recovered to normal range.
Fanconi a nemia–associated neutropenia: Note: Should only be used to manage neutropenia associated with recurrent or serious infections (particularly if the ANC is persistently <500/mm3) or for a short time while awaiting hematopoietic cell transplantation (Ref). Some centers reserve for patients with ANC <200/mm3 or those with invasive infection (bacterial or fungal) and ANC <1,000/mm3 (Ref).
Initial: SUBQ: 5 mcg/kg/day; titrate to target ANC 1,500 to 2,000/mm3 and transition to every-other-day dosing if possible; discontinue if ANC does not improve after 8 weeks (Ref).
Hematopoietic cell mobilization in healthy donors for peripheral blood stem cells allogeneic transplantation (off-label use): SUBQ: 10 mcg/kg once daily for 5 days, followed by apheresis on day 5 or on days 5 and 6 (Ref) or ~10 mcg/kg once daily for 4 consecutive days (for recipients <35 kg) or for 5 consecutive days (for recipients ≥35 kg) followed by apheresis on day 5 or on days 5 and 6; the administered dose was rounded to filgrastim vial sizes of 300 mcg or 480 mcg (total daily dose was ≤~13.3 mcg/kg/day) (Ref).
Hematopoie tic cell mobilization prior to betibeglogene autotemcel in beta thalassemia (off-label use): Note: Decrease filgrastim dose by 50% for WBC >100,000/mm3 prior to the day of apheresis. Refer to protocol for further mobilization and apheresis details.
Patients with an intact spleen: SUBQ: 10 mcg/kg once daily in the morning on mobilization days 1 to 5 (and days 6 and 7 if needed), followed by apheresis, which usually begins on mobilization day 5 (Ref).
Patients without an intact spleen: SUBQ: 5 mcg/kg once daily in the morning on mobilization days 1 to 5 (and days 6 and 7 if needed), followed by apheresis, which usually begins on mobilization day 5 (Ref).
Hematopoietic radiation injury syndrome, acute (Neupogen): SUBQ : 10 mcg/kg once daily; begin as soon as possible after suspected or confirmed radiation doses >2 gray (Gy) and continue filgrastim until ANC remains >1,000/mm3 for 3 consecutive CBCs or ANC exceeds 10,000/mm3 after the radiation-induced nadir. The American Society of Clinical Oncology guidelines recommend initiating within 24 hours of exposure of a dose ≥2 Gy and/or significant decrease in absolute lymphocyte count, or for anticipated neutropenia <500/mm3 for ≥7 days (Ref).
Hepatitis C treatment–associated neutropenia (off-label use): SUBQ : 150 mcg once weekly to 300 mcg 3 times weekly; titrate to maintain ANC between 750 and 10,000/mm3 (Ref).
Neutropenia in advanced HIV infection (off-label use): SUBQ : Initial: 1 mcg/kg once daily or 300 mcg one to three times per week; titrate to maintain ANC 2,000 to 10,000/mm3; doses up to 10 mcg/kg/day or 600 mcg daily were studied (Ref).
Peripheral blood progenitor cell collection and therapy (Neupogen and filgrastim biosimilars Nivestym and Zarxio): SUBQ: 10 mcg/kg daily, usually for 6 to 7 days (with apheresis occurring on days 5, 6, and 7). Begin at least 4 days before the first apheresis and continue until the last apheresis; discontinue for WBC >100,000/mm3.
Off-label combination therapy
In combination with plerixafor (non-Hodgkin lymphoma or multiple myeloma ): SUBQ: 10 mcg/kg once daily (in combination with plerixafor); begin 4 days before initiation of plerixafor; continue G-CSF on each day prior to apheresis until specified collection goals are met or a maximum total duration of 8 days (Ref).
In combination with motixafortide (multiple myeloma): SUBQ: 10 mcg/kg once daily (in combination with motixafortide); begin 4 days before initiation of motixafortide; continue G-CSF on each day prior to apheresis until specified collection goals are met or a maximum total duration of 8 days (Ref).
Severe chronic neutropenia (Neupogen and filgrastim biosimilars):
Congenital: SUBQ: Initial: 6 mcg/kg/day in 2 divided doses; adjust the dose based on ANC and clinical response; mean dose: 6 mcg/kg/day.
Idiopathic: SUBQ: Initial: 5 mcg/kg once daily; adjust the dose based on ANC and clinical response; total daily dose may be administered in 1 or 2 divided doses; mean dose: 1.2 mcg/kg/day.
Cyclic: SUBQ: Initial: 5 mcg/kg once daily; adjust the dose based on ANC and clinical response; total daily dose may be administered in 1 or 2 divided doses; mean dose: 2.1 mcg/kg/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Kidney impairment at treatment initiation:
Neupogen, filgrastim-biosimilars, and tbo-filgrastim:
Altered kidney function: No dosage adjustment necessary for any degree of kidney impairment (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzed (large molecular weight): No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Unlikely to be dialyzed (large molecular weight): No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
Nephrotoxicity during treatment:
Glomerulonephritis due to filgrastim: If glomerulonephritis is suspected, evaluate for cause; if likely due to filgrastim, consider dose reduction or treatment interruption.
Neupogen and filgrastim biosimilars: No dosage adjustment necessary.
Tbo-filgrastim: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Acute respiratory distress syndrome: Evaluate patients with pulmonary symptoms such as fever, pulmonary infiltrates, or respiratory distress for acute respiratory distress syndrome (ARDS); discontinue filgrastim if ARDS occurs.
Allergic reactions (serious): Permanently discontinue filgrastim; may be managed symptomatically with administration of antihistamines, steroids, bronchodilators, and/or epinephrine.
Aortitis (suspected): Discontinue filgrastim if aortitis is suspected.
Capillary leak syndrome: Monitor closely and manage symptomatically if capillary leak syndrome develops (may require intensive care).
Cutaneous vasculitis: Withhold filgrastim if cutaneous vasculitis occurs; may be restarted with a dose reduction once symptoms resolve and the ANC has decreased.
Sickle cell crises: Discontinue filgrastim if sickle cell crisis occurs.
Splenic rupture (symptoms): Withhold filgrastim and evaluate for enlarged spleen or splenic rupture; discontinue with confirmed or suspected splenic rupture.
Refer to adult dosing.
(For additional information see "Filgrastim (including biosimilars): Pediatric drug information")
Dosage guidance:
Dosing: International considerations: Dosages below expressed as micrograms; 1 mcg = 100,000 units (Ref). Dosing may vary by protocol; refer to specific treatment protocol. For larger doses (eg, adolescents), rounding doses to the nearest vial size may enhance patient convenience and reduce costs without compromising clinical response.
Bone marrow transplantation: Filgrastim and filgrastim biosimilars: Children and Adolescents: IV infusion: 10 mcg/kg/day (administer ≥24 hours after chemotherapy and ≥24 hours after bone marrow infusion); adjust the dose according to the duration and severity of neutropenia; dosage adjustment recommended based on neutrophil response:
When ANC >1,000/mm3 for 3 consecutive days: Reduce dose to 5 mcg/kg/day
If ANC remains >1,000/mm3 for 3 more consecutive days: Discontinue
If ANC decreases to <1,000/mm3: Resume at 5 mcg/kg/day
If ANC decreases to <1,000/mm3 during the 5 mcg/kg/day dose, increase dose to 10 mcg/kg/day and follow the above steps
Bone marrow transplantation, slow engraftment: Filgrastim: Infants, Children, and Adolescents: Limited data available: IV, SubQ: 5 mcg/kg/day administered ≥24 hours after cytotoxic chemotherapy and ≥24 hours after bone marrow infusion (Ref).
Chemotherapy-induced neutropenia (myelosuppressive chemotherapy recipients with non-myeloid malignancies):
Filgrastim and filgrastim biosimilars: Infants, Children, and Adolescents: IV, SubQ: 5 mcg/kg/day once daily beginning ≥24 hours after chemotherapy; recommendations for duration of therapy vary: Manufacturer labeling is for up to 14 days or until ANC reaches 10,000/mm3; others have suggested a lower target ANC of 5,000/mm3 (Ref); review treatment-specific protocol for guidance. For subsequent chemotherapy cycles, dose may be increased by 5 mcg/kg based upon patient's previous response to therapy along with duration and severity of neutropenia.
Tbo-Filgrastim (Granix): Infants, Children, and Adolescents: SubQ: 5 mcg/kg/day once daily; begin ≥24 hours after chemotherapy and continue until anticipated nadir has passed and neutrophil count has recovered to normal range.
Hematopoietic syndrome of acute radiation syndrome, acute: Filgrastim: Infants, Children, and Adolescents: SubQ: 10 mcg/kg/day once daily; begin as soon as possible after suspected or confirmed radiation doses >2 gray (Gy) and continue filgrastim until ANC remains >1,000/mm3 for 3 consecutive CBCs or ANC exceeds 10,000/mm3 after the radiation-induced nadir. ASCO guidelines recommend initiating within 24 hours of exposure of a dose ≥2 Gy and/or significant decrease in absolute lymphocyte count, or for anticipated neutropenia <500/mm3 for ≥7 days (Ref).
Neutropenia, severe, chronic: Filgrastim and filgrastim biosimilars: Infants, Children, and Adolescents: SubQ:
Congenital: Initial: 6 mcg/kg/day in 2 divided doses; adjust the dose based on ANC and clinical response; median dose: 6 mcg/kg/day
Idiopathic: Initial: 5 mcg/kg/day in 1 or 2 divided doses; adjust the dose based on ANC and clinical response; median dose: 1.2 mcg/kg/day
Cyclic: Initial: 5 mcg/kg/day in 1 or 2 divided doses; adjust the dose based on ANC and clinical response; median dose: 2.1 mcg/kg/day
Neutropenia in HIV infection (eg, drug induced): Limited data available:
Note: Trials performed with Neupogen product
Infants and Children: SubQ: Initial: 1 mcg/kg/day, titrate every 3 days to maintain desired ANC. Doses as high as 20 mcg/kg/day have been described (Ref).
Adolescents:
Weight-based dosing: SubQ: Initial: 1 mcg/kg/day, titrate every 3 days to maintain desired ANC. Doses as high as 20 mcg/kg/day have been described (Ref).
Fixed dosing: SubQ: Initial: 300 mcg 1 to 3 times weekly, titrate to desired ANC. Maximum daily dose: 600 mcg/day (Ref).
Peripheral blood progenitor cell collection and therapy: Filgrastim and filgrastim biosimilars: Infants, Children, and Adolescents: Limited data in infants: SubQ, IV: 10 mcg/kg/day; begin at least 4 days prior to first apheresis and continue until apheresis; discontinue if WBC >100,000/mm3 (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Baseline impairment at initiation:
Filgrastim and filgrastim biosimilars: No dosage adjustment necessary
Tbo-filgrastim:
Mild impairment: No dosage adjustment necessary
Moderate to severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Renal toxicity during therapy:
Filgrastim, filgrastim biosimilars, or tbo-filgrastim: Glomerulonephritis due to filgrastim products: Consider dose reduction or interrupt treatment
Filgrastim and filgrastim biosimilars: No dosage adjustment necessary
Tbo-filgrastim: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Life-threatening acute respiratory distress syndrome (ARDS) has been reported. Most cases occur in neutropenic patients, but ARDS has also been reported in non-neutropenic patients (Ref). Interstitial pneumonia and pleural effusion have also been reported (Ref).
Mechanism: Related to pharmacologic action; increased neutrophils cause injury to the alveolar capillary wall (Ref). May also enhance functions of macrophages, monocytes, and endothelial cells via granulocyte colony-stimulating factors (G-CSF) receptors, potentially regulating cytokine production and feedback (Ref).
Onset: Varied; in neutropenic patients, may occur during neutrophil recovery or 1 to 11 days after neutrophil recovery (Ref). In non-neutropenic patients, reported after 5 days of treatment (Ref).
Risk factors:
• Pneumonia prior to neutropenia recovery (Ref)
• Rate of leukocyte count elevation after neutropenia recovery (Ref)
Aortitis has been reported in patients receiving granulocyte colony-stimulating factors (G-CSF), including filgrastim (Ref). Manifestations of aortitis may include generalized fever, abdominal pain, malaise, back pain, and increased inflammatory markers (eg, c-reactive protein, WBC count). G-CSF–induced aortitis may occur in the thoracic to abdominal aorta but most commonly presents in the aortic arch (Ref). Resolution of reported cases of aortitis associated with filgrastim have ranged from 1 to 15 months (Ref).
Mechanism: Not clearly established; may be caused by pro-inflammatory reaction and neutrophil-mediated damage (Ref). G-CSF can cause autoimmune reactions via IL-6 between Th17 cells and CD4+ T cells, leading to aortitis (Ref).
Onset: Varied; most reported cases associated with filgrastim occurred 6 to 13 days post administration; however, one case occurred 1 year post administration (Ref).
Risk factors:
• Concurrent taxane use (Ref)
• East Asian decent (Ref)
Potentially life-threatening capillary leak syndrome (CLS), characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration, may occur in patients receiving human granulocyte colony-stimulating factors (G-CSF), including filgrastim. CLS episodes may vary in frequency and severity; of the 14 cases of filgrastim-associated CLS, 12 (86%) were categorized as serious and 5 (36%) were fatal (Ref).
Mechanism: Not clearly established; increase in cytokine production from G-CSF may lead to vascular permeability. Inflammatory process from leukocytosis leading to capillary leak from G-CSF has been suggested (Ref).
Onset: Varied; median 8 days after administration (Ref).
Moderate or severe cutaneous vasculitis (ie, hypersensitivity angitis) has been reported. Some form of vasculitis occurred in 4.1% of patients with severe chronic neutropenia (SCN) receiving long-term therapy (Ref). Resolution occurs with discontinuation, and most patients can continue treatment at the same dose or a reduced dose (Ref).
Mechanism: Related to pharmacologic action; increased neutrophil count and secondary cytokine release (Ref).
Onset: Varied; cases have been reported within 3 to 4 days after initiation of therapy (Ref) and after long-term therapy.
Risk factors:
• Long-term therapy in patients with SCN
Glomerulonephritis, including rapidly progressive glomerulonephritis has occurred in patients receiving filgrastim. Glomerulonephritis usually resolved after filgrastim dose reduction or discontinuation; however, some cases have persisted and/or resulted in systemic involvement and the development of renal failure (Ref). Henoch-Schönlein purpura associated with glomerulonephritis has also been reported (Ref).
Mechanism: Not clearly established; one hypothesis is that granulocyte colony-stimulating factors (G-CSF) injures endothelial cells, resulting in vasculitis, potentially leading to glomerular basement membrane injury (Ref).
Onset: Varied; reported after 1 month to several months (Ref).
Immediate hypersensitivity reactions, including anaphylaxis, angioedema, and urticaria may occur (Ref). Delayed cutaneous hypersensitivity reactions, ranging from a maculopapular rash to Sweet syndrome, have also been reported (Ref).
Mechanism: Immediate hypersensitivity reactions: Unknown. In some patients, reactions may be IgE-mediated (Ref); however, other cases occur with initial exposure, suggesting a non-IgE-mediated mechanism (Ref). Polysorbate-80, used as a carrier in filgrastim formulations, may be responsible for some hypersensitivity reactions (Ref).
Onset: Immediate hypersensitivity reactions: Rapid; typically occurred within 90 minutes of administration (Ref); although also reported up to 5 hours (Ref). Delayed hypersensitivity reactions: Occurred within ~14 days of administration (Ref).
Risk factors:
• Cross-reactivity between granulocyte colony-stimulating factor (G-CSF) formulations (eg, filgrastim, pegfilgrastim and biosimilars) is unknown (Ref). Patients with immediate hypersensitivity reactions to polysorbate 80 may be cross-reactive to polyethylene glycol (Ref).
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have been associated with filgrastim when used with chemotherapy and/or radiotherapy in patients with breast or lung cancer, or non-Hodgkin lymphoma (NHL) (Ref). Cytogenetic abnormalities and transformation to MDS and AML have also been observed in patients with severe chronic neutropenia (SCN) receiving granulocyte colony-stimulating factors (G-CSF), including filgrastim (Ref). MDS and AML have also occurred in patients with SCN without G-CSF therapy.
Mechanism: Unknown; in malignancies, suggested mechanisms include leukemogenesis potentiation in hematopoietic cells that are damaged by chemotherapy (Ref) and G-CSF allowing more intensive chemotherapy to be given more frequently and with fewer dose reductions increasing total exposure (Ref). In SCN, G-CSF may rescue malignant cells and/or may cause marrow progenitors to acquire new mutations. G-CSF also prolongs patient survival in SCN, potentially allowing time for the malignant predisposition of SCN to occur (Ref).
Onset: Varied; in malignancies, onset varied from 1 to 10 years postexposure to G-CSF (Ref). In SCN, duration of G-CSF to MDS to AML ranged from 1 month to 8.4 years (Ref).
Risk factors:
• Concurrent use with anthracycline or alkylating agent in breast or lung cancer (Ref)
• Ten or more doses of filgrastim was associated with a higher risk of development of MDS/AML in patients with NHL (Ref)
• Prior radiation therapy (Ref)
Precipitation of sickle cell crisis leading to acute multiorgan failure syndrome has been reported; may be fatal (Ref).
Mechanism: Related to pharmacologic action (ie, increased neutrophil count and activation). Neutrophils likely contribute to microvascular sickle cell trapping leading to vasoocclusion (Ref).
Onset: Rapid; onset of symptoms occurred 3 to 4 days after initiation of granulocyte colony-stimulating factor (G-CSF) (Ref).
Risk factors:
• Increased Hb S levels; G-CSF has been administered safely for mobilization in patients with sickle cell trait with lower Hb S levels (35% to 40%), possibly suggesting a threshold that higher Hb S levels may predispose patients to G-CSF-induced sickle cell crisis. While no major complications were reported, these patients experienced higher symptom scores and required more analgesics (Ref).
Rare cases of splenic rupture have been reported with granulocyte colony-stimulating factor (G-CSF) use for hematology/oncology indications and in healthy donors; may be fatal (Ref).
Mechanism: Related to pharmacologic action; G-CSF causes a significant increase of immune myeloid cell density in the spleen through extramedullary hematopoiesis, potentially causing splenic rupture (Ref).
Onset: Varied; reported 2 to 10 days into therapy (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Percentages reported as monotherapy and as part of combination chemotherapy regimens. As reported in adults, unless otherwise noted.
>10%:
Cardiovascular: Chest pain (13%)
Dermatologic: Skin rash (14%)
Gastrointestinal: Nausea (43%)
Hematologic & oncologic: Thrombocytopenia (infants, children, adolescents, and adults: 34% to 38%)
Hepatic: Increased serum alkaline phosphatase (6% to 11%)
Nervous system: Dizziness (14%), fatigue (20%), pain (12%)
Neuromuscular & skeletal: Back pain (15%), ostealgia (3% to 30%)
Respiratory: Cough (14%), dyspnea (13%)
Miscellaneous: Fever (infants, children, adolescents, and adults: 8% to 48%)
1% to 10%:
Cardiovascular: Hypertension (≥5%)
Dermatologic: Alopecia (≥5%), erythema of skin (≥2%), maculopapular rash (≥2%)
Endocrine & metabolic: Increased lactate dehydrogenase (6%)
Gastrointestinal: Diarrhea (infants, children, adolescents, and adults: 6%)
Genitourinary: Urinary tract infection (≥5%)
Hematologic & oncologic: Anemia (≥5%), leukocytosis (≤2%), splenomegaly (≥5%)
Hypersensitivity: Hypersensitivity reaction (≥5%; including severe hypersensitivity reactions)
Immunologic: Antibody development (infants, children, adolescents, and adults: 1% to 3%; no evidence of neutralizing response)
Infection: Sepsis (≥5%)
Nervous system: Headache (infants, children, adolescents, and adults: 6% to 10%), hypoesthesia (≥5%), insomnia (≥5%)
Neuromuscular & skeletal: Arthralgia (9%), limb pain (infants, children, adolescents, and adults: 6% to 7%), muscle spasm (≥5%), musculoskeletal pain (≥5%)
Respiratory: Bronchitis (≥5%), epistaxis (≥2%), upper respiratory tract infection (≥5%)
Postmarketing:
Cardiovascular: Capillary leak syndrome (Izzedine 2022), vasculitis (aortitis) (Lardieri 2018)
Dermatologic: Sweet syndrome (White 2006), urticaria (Nuñez-Acevedo 2015)
Hematologic & oncologic: Abnormal erythropoiesis (extramedullary hematopoiesis), hemophagocytic lymphohistiocytosis (Higuchi 2023), Henoch-Schönlein purpura (Dale 2003), sickle cell crisis (Grigg 2001), splenic rupture (Veerappan 2007)
Hypersensitivity: Anaphylaxis (Doval 2019), angioedema (Martin Munoz 1996), hypersensitivity angiitis (Yoon 2020)
Nervous system: Asthenia
Neuromuscular & skeletal: Decreased bone mineral density, myalgia, osteoporosis, rhabdomyolysis (Hacioglu 2009)
Renal: Glomerulonephritis (Dale 2003)
Respiratory: Acute respiratory distress syndrome (Azoulay 2001), hemoptysis, pleural effusion (Azoulay 2001), pneumonia (interstitial) (Azoulay 2001), pulmonary alveolar hemorrhage, pulmonary infiltrates
History of serious allergic reactions to human granulocyte colony-stimulating factors, such as filgrastim or pegfilgrastim, or any component of the formulation.
Canadian labeling: Additional contraindications (not in the US labeling): Known hypersensitivity to E. coli-derived products.
Concerns related to adverse reactions:
• Hematologic effects: White blood cell counts of ≥100,000/mm3 have been reported with filgrastim doses >5 mcg/kg/day. Doses that increase the ANC beyond 10,000/mm3 may not result in additional clinical benefit. In patients receiving myelosuppressive chemotherapy, filgrastim discontinuation generally resulted in a 50% decrease in circulating neutrophils within 1 to 2 days, and a return to pretreatment levels in 1 to 7 days. Thrombocytopenia has also been reported with filgrastim products.
Disease-related concerns:
• Severe chronic neutropenia: Establish diagnosis of severe chronic neutropenia (SCN) prior to initiation; use prior to appropriate diagnosis of SCN may impair or delay proper evaluation and treatment for neutropenia due to conditions other than SCN.
Special populations:
• Pediatric patients: Colony-stimulating factor (CSF) use in pediatric patients is typically directed by clinical pediatric protocols. The ASCO Recommendations for the Use of WBC Growth Factors Clinical Practice Guideline Update states that CSFs may be reasonable as primary prophylaxis in pediatric patients when chemotherapy regimens with a high likelihood of febrile neutropenia are employed. Likewise, secondary CSF prophylaxis should be limited to high-risk patients. In pediatric cancers in which dose-intense chemotherapy (with a survival benefit) is used, CSFs should be given to facilitate chemotherapy administration. CSFs should not be used in the pediatric population for non-relapsed acute lymphoblastic or myeloid leukemia when no infection is present (ASCO [Smith 2015]).
• Radiation therapy recipients: Avoid concurrent radiation therapy with filgrastim products; safety and efficacy have not been established with patients receiving radiation therapy.
Dosage form specific issues:
• Latex: The packaging of some dosage forms may contain latex.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Other warnings/precautions:
• International issues: Some products available internationally may have vial strength and dosing expressed as units (instead of as micrograms). Refer to prescribing information for specific strength and dosing information.
• Nuclear imaging: Increased bone marrow hematopoietic activity due to colony-stimulating factor use has been associated with transient positive bone-imaging changes; interpret results accordingly.
• Tumor growth effects: The G-CSF receptor through which filgrastim products act has been found on tumor cell lines. May potentially act as a growth factor for any tumor type (including myeloid malignancies and myelodysplasia). When used for stem cell mobilization, may release tumor cells from marrow, which could be collected in leukapheresis product; potential effect of tumor cell reinfusion is unknown.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Injection:
Neupogen: filgrastim 300 mcg/mL (1 mL); filgrastim 480 mcg/1.6 mL (1.6 mL) [contains polysorbate 80]
Releuko: Filgrastim-ayow 480 mcg/1.6 mL (300 mcg/mL) (1.6 mL [DSC]) [contains polysorbate 80]
Solution, Injection [preservative free]:
Nivestym: filgrastim-aafi 300 mcg/mL (1 mL); filgrastim-aafi 480 mcg/1.6 mL (1.6 mL) [contains polysorbate 80]
Releuko: Filgrastim-ayow 300 mcg/mL (1 mL [DSC]) [contains polysorbate 80]
Solution, Subcutaneous [preservative free]:
Granix: tbo-filgrastim 300 mcg/mL (1 mL); tbo-filgrastim 480 mcg/1.6 mL (1.6 mL) [contains polysorbate 80]
Solution Prefilled Syringe, Injection [preservative free]:
Neupogen: filgrastim 300 mcg/0.5 mL (0.5 mL); filgrastim 480 mcg/0.8 mL (0.8 mL) [contains polysorbate 80]
Nivestym: filgrastim-aafi 300 mcg/0.5 mL (0.5 mL); filgrastim-aafi 480 mcg/0.8 mL (0.8 mL) [contains polysorbate 80]
Zarxio: filgrastim-sndz 300 mcg/0.5 mL (0.5 mL); filgrastim-sndz 480 mcg/0.8 mL (0.8 mL) [contains polysorbate 80]
Solution Prefilled Syringe, Subcutaneous [preservative free]:
Granix: tbo-filgrastim 300 mcg/0.5 mL (0.5 mL); tbo-filgrastim 480 mcg/0.8 mL (0.8 mL) [contains polysorbate 80]
Releuko: Filgrastim-ayow 300 mcg/0.5 mL (0.5 mL); Filgrastim-ayow 480 mcg/0.8 mL (0.8 mL) [contains polysorbate 80]
Yes
Solution (Granix Subcutaneous)
300 mcg/mL (per mL): $299.84
480 mcg/1.6 mL (per mL): $299.91
Solution (Neupogen Injection)
300 mcg/mL (per mL): $377.80
480 mcg/1.6 mL (per mL): $376.00
Solution (Nivestym Injection)
300 mcg/mL (per mL): $262.80
480 mcg/1.6 mL (per mL): $262.80
Solution Prefilled Syringe (Granix Subcutaneous)
300 mcg/0.5 mL (per 0.5 mL): $299.84
480 mcg/0.8 mL (per 0.8 mL): $479.87
Solution Prefilled Syringe (Neupogen Injection)
300 mcg/0.5 mL (per 0.5 mL): $400.44
480 mcg/0.8 mL (per 0.8 mL): $637.72
Solution Prefilled Syringe (Nivestym Injection)
300 mcg/0.5 mL (per 0.5 mL): $262.80
480 mcg/0.8 mL (per 0.8 mL): $420.48
Solution Prefilled Syringe (Zarxio Injection)
300 mcg/0.5 mL (per 0.5 mL): $329.24
480 mcg/0.8 mL (per 0.8 mL): $526.78
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection:
Neupogen: filgrastim 300 mcg/mL (1 mL, 1.6 mL) [contains polysorbate 80]
Nivestym: filgrastim 300 mcg/mL (1 mL); filgrastim 480 mcg/1.6 mL (1.6 mL) [contains polysorbate 80]
Solution Prefilled Syringe, Injection:
Grastofil: filgrastim 300 mcg/0.5 mL (0.5 mL); filgrastim 480 mcg/0.8 mL (0.8 mL) [contains polysorbate 80]
Neupogen: filgrastim 300 mcg/0.5 mL (0.5 mL); filgrastim 480 mcg/0.8 mL (0.8 mL) [contains polysorbate 80]
Nivestym: filgrastim 300 mcg/0.5 mL (0.5 mL); filgrastim 480 mcg/0.8 mL (0.8 mL) [contains polysorbate 80]
Do not administer earlier than 24 hours after or in the 24 hours prior to cytotoxic chemotherapy.
IV (Neupogen and filgrastim biosimilars): May be administered IV as a short infusion over 15 to 30 minutes (chemotherapy-induced neutropenia) or by continuous infusion (chemotherapy-induced neutropenia) or as an infusion of no longer than 24 hours (bone marrow transplantation).
SUBQ: May be administered SUBQ (chemotherapy-induced neutropenia, peripheral blood progenitor cell collection, severe chronic neutropenia, hematopoietic radiation injury syndrome). Administer into the outer upper arm, abdomen (except within 2 inches of navel), front middle thigh, or the upper outer buttocks area. Rotate injection site; do not inject into areas that are tender, red, bruised, hardened, scaly, or scarred, or sites with stretch marks.
Some patients (or caregivers) may be appropriate candidates for SUBQ self-administration with proper training; patients/caregivers should follow the manufacturer instructions for preparation and administration. Do not skip doses, change schedule, or discontinue without consulting with health care provider. Some products are available in prefilled syringes either with or without a needle guard; prefilled syringes without a safety needle guard are intended for patient/caregiver self-administration. Prefilled syringes with a safety needle guard are not designed to allow for direct administration of doses <0.3 mL (180 mcg); use vials for doses <0.3 mL (180 mcg). If filgrastim comes in contact with the skin, wash area thoroughly with soap and water; if eye contact occurs, flush exposed eye(s) with water.
Parenteral: Allow product to reach room temperature prior to use; after removal from refrigerator wait a minimum of 30 minutes and maximum of 24 hours; discard after out of the refrigerator >24 hours. Nivestym and Zarxio syringes are not recommended for direct administration of doses <0.3 mL; dose cannot be accurately measured.
SubQ: Administer into the outer upper arm, abdomen (except within 2 inches of navel), front middle thigh, or the upper outer buttocks area. Rotate injection site; do not inject into areas that are tender, red, bruised, hardened, or scarred, or sites with stretch marks. Do not administer earlier than 24 hours after or in the 24 hours prior to cytotoxic chemotherapy.
IV: Neupogen (Vial only), Nivestym (Vial only), Zarxio:
Chemotherapy-induced neutropenia: Administer IV over 15 to 30 minutes; may also be administered as a continuous infusion. Do not administer earlier than 24 hours after or in the 24 hours prior to cytotoxic chemotherapy.
Bone marrow transplantation: Administer as an IV infusion over ≤24 hours. Administer ≥24 hours after chemotherapy and ≥24 hours after bone marrow infusion.
Chemotherapy-induced myelosuppression in nonmyeloid malignancies:
Neupogen and filgrastim biosimilars: To decrease the incidence of infection (neutropenic fever) in patients with nonmyeloid malignancies receiving myelosuppressive chemotherapy associated with a significant incidence of severe neutropenia with fever.
Tbo-filgrastim: To decrease the duration of severe neutropenia in adult and pediatric patients ≥1 month of age with nonmyeloid malignancies receiving myelosuppressive chemotherapy associated with a clinically significant incidence of neutropenic fever.
Acute myeloid leukemia following induction or consolidation chemotherapy (Neupogen and filgrastim biosimilars): To reduce the time to neutrophil recovery and the duration of fever following induction or consolidation chemotherapy in adults with acute myeloid leukemia.
Bone marrow transplantation (Neupogen and filgrastim biosimilars): To reduce the duration of neutropenia and neutropenia-related events (eg, neutropenic fever) in patients with nonmyeloid malignancies receiving myeloablative chemotherapy followed by marrow transplantation.
Hematopoietic radiation injury syndrome, acute (Neupogen): To increase survival in patients acutely exposed to myelosuppressive doses of radiation.
Peripheral blood progenitor cell collection and therapy (Neupogen and filgrastim biosimilars Nivestym and Zarxio): Mobilization of autologous hematopoietic progenitor cells into the peripheral blood for apheresis collection.
Severe chronic neutropenia (Neupogen and filgrastim biosimilars): Long-term administration to reduce the incidence and duration of neutropenic complications (eg, fever, infections, oropharyngeal ulcers) in symptomatic patients with congenital, cyclic, or idiopathic neutropenia.
Note: Nivestym (filgrastim-aafi), Releuko (filgrastim-ayow), and Zarxio (filgrastim-sndz) are approved as biosimilars to Neupogen (filgrastim). In Canada, Grastofil is a biosimilar to Neupogen (filgrastim).
Alcoholic hepatitis, severe; Fanconi anemia–associated neutropenia; Hematopoietic cell mobilization in healthy donors for peripheral blood stem cells for allogeneic transplantation; Hematopoietic cell mobilization prior to betibeglogene autotemcel in beta thalassemia; Myelodysplastic syndrome–associated anemia; Neutropenia in advanced HIV infection; Neutropenia, hepatitis C treatment–associated
Filgrastim may be confused with efbemalenograstim alfa, eflapegrastim, pegfilgrastim, sargramostim, tbo-filgrastim.
Neupogen may be confused with Epogen, Neulasta, Nutramigen.
Neupogen [US, Canada, and multiple international markets] may be confused with Neupro brand name for rotigotine [multiple international markets].
Some products available internationally may have vial strength and dosing expressed as units (instead of as micrograms). Refer to prescribing information for specific strength and dosing information.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Belotecan: Granulocyte Colony-Stimulating Factors may enhance the neutropenic effect of Belotecan. Management: Do not administer granulocyte colony-stimulating factor (G-CSF) until at least 24 hours after completion of belotecan administration. Monitor neutrophil counts and signs/symptoms of neutropenic fever in patients receiving this combination. Risk D: Consider therapy modification
Betibeglogene Autotemcel: Granulocyte Colony-Stimulating Factors may interact via an unknown mechanism with Betibeglogene Autotemcel. Management: Granulocyte-colony stimulating factor is not recommended for 21 days after betibeglogene autotemcel infusion. Risk X: Avoid combination
Bleomycin: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Bleomycin. Specifically, the risk for pulmonary toxicity may be increased. Management: Avoid use of granulocyte colony-stimulating factors 24 hours before (14 days for pegfilgrastim) and 24 hours after the last dose of bleomycin. Risk D: Consider therapy modification
CycloPHOSphamide: Filgrastim may enhance the adverse/toxic effect of CycloPHOSphamide. Specifically, the risk of pulmonary toxicity may be enhanced. Risk C: Monitor therapy
Exagamglogene Autotemcel: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Exagamglogene Autotemcel. Risk X: Avoid combination
Lovotibeglogene Autotemcel: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Lovotibeglogene Autotemcel. Risk X: Avoid combination
Tisagenlecleucel: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Tisagenlecleucel. Risk X: Avoid combination
Topotecan: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Topotecan. Specifically, the risk for the development of interstitial lung disease may be increased. Granulocyte Colony-Stimulating Factors may enhance the myelosuppressive effect of Topotecan. Management: Avoid use of granulocyte colony-stimulating factors 24 hours before (14 days for pegfilgrastim) and 24 hours after the last dose of topotecan. Additionally, monitor patients closely for the development of interstitial lung disease with this combination. Risk D: Consider therapy modification
Filgrastim crosses the placenta.
Available data do not suggest an association between the use of filgrastim during pregnancy and an increased risk of miscarriage, preterm labor, or adverse fetal outcomes (birth weight or infection) following maternal use for severe chronic neutropenia. Outcome data related to the use of granulocyte-colony stimulating factor (G-CSF) in pregnant patients with congenital, cyclic, or idiopathic neutropenia (Boxer 2015; Zeidler 2014), G-CSF-induced allogeneic peripheral blood stem cells donation (Leitner 2001; Shibata 2003), or chemotherapy-induced neutropenia during pregnancy (Berends 2021; Cardonick 2012) are limited.
Data collected from the Severe Chronic Neutropenia International Registry (SCNIR) note dosing for chronic conditions may need adjusted in pregnant patients; the lowest effective dose to maintain the absolute neutrophil count is recommended (Zeidler 2014).
G-CSF is recommended for pregnant patients who required G-CSF for chronic neutropenia prior to pregnancy and those treated for severe congenital neutropenia; frequent monitoring is recommended, particularly in patients with autoimmune neutropenia. Monitor neutrophil count of the newborn following delivery (Fioredda 2023). Consensus panel guidelines for hematologic malignancies during pregnancy suggest that although data are limited, administration of granulocyte growth factors during pregnancy may be acceptable (Lishner 2016). One review suggests when utilizing for hematopoietic stem cell mobilization (in healthy donors; not a labeled use) avoiding use during the first trimester until additional outcome information is available (Pessach 2013).
Endogenous G-CSF can be detected in breast milk (Calhoun 2003).
G-CSF concentrations are increased for at least 3 days following maternal filgrastim administration (Kaida 2007). Recombinant G-CSF, when administered orally to infants, was not found to be absorbed (Calhoun 2003).
Adverse events were not observed in breastfeeding infants following maternal use of filgrastim (limited data). According to some manufacturers, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother, as well as the mother's underlying condition. Due to the potential for serious adverse events in a breastfed infant, the manufacturer of tbo-filgrastim does not recommend breastfeeding during therapy and for 2 weeks after the last tbo-filgrastim dose.
Some products may contain sodium.
Chemotherapy-induced neutropenia: CBC with differential and platelets prior to chemotherapy and twice weekly during growth factor treatment.
Bone marrow transplantation: CBC with differential and platelets frequently.
Hematopoietic radiation injury syndrome (acute): CBC at baseline (do not delay filgrastim for baseline CBC) and approximately every 3 days until ANC remains >1,000/mm3 for 3 consecutive CBCs. Estimate absorbed radiation dose (radiation exposure) based on information from public health authorities, biodosimetry (if available), or clinical findings (eg, onset of vomiting or lymphocyte depletion kinetics).
Peripheral progenitor cell collection: Neutrophil counts after 4 days of filgrastim treatment.
Severe chronic neutropenia: CBC with differential and platelets twice weekly during the first month of therapy and for 2 weeks following dose adjustments; once clinically stable, monthly for 1 year and quarterly thereafter. Monitor bone marrow and karyotype prior to treatment; and monitor marrow and cytogenetics annually throughout treatment.
Neutropenia in advanced HIV infection (off-label use): ANC 3 times weekly for 1st week then weekly thereafter (Kuritzkes 1999).
All patients: Monitor for signs/symptoms of acute respiratory distress syndrome (evaluate patients who develop fever/lung infiltrates or respiratory distress), allergic reactions, aortitis, capillary leak syndrome, cutaneous vasculitis, myelodysplastic syndrome and acute myeloid leukemia, and splenic rupture (eg, upper abdominal pain, left upper quadrant pain, or shoulder tip pain).
Filgrastim is a granulocyte colony-stimulating factor (G-CSF) produced by recombinant DNA technology. G-CSFs stimulate the production, maturation, and activation of neutrophils to increase both their migration and cytotoxicity.
Onset of action:
Filgrastim: Transient increase in neutrophil count is seen 1 to 2 days after filgrastim initiation.
Tbo-filgrastim: Time to maximum ANC: 3 to 5 days.
Duration:
Filgrastim: Neutrophil counts generally return to baseline within 4 days.
Tbo-filgrastim: ANC returned to baseline by 21 days after completion of chemotherapy.
Distribution: Vd: 150 mL/kg; Continuous infusion: No evidence of drug accumulation over a 11- to 20-day period.
Metabolism: Systemically degraded
Bioavailability: Filgrastim: SUBQ: 60% to 70%; Tbo-filgrastim: SUBQ: 33%.
Half-life elimination:
Neonates: 4.4 ± 0.4 hours (Gillan 1994).
Adults: Filgrastim: ~3.5 hours; Tbo-filgrastim: 3 to 3.5 hours.
Time to peak, serum: SUBQ: Filgrastim: 2 to 8 hours; Tbo-filgrastim: 4 to 6 hours.
Altered kidney function: In a study with healthy volunteers, subjects with moderate renal impairment, and subjects with end-stage renal disease (ESRD) (n=4 per group), higher serum concentrations were observed in subjects with ESRD.
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