Version June 2023
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. May round the dose to the nearest vial size for convenience and cost minimization (Ref). 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). International considerations: Dosages below expressed as micrograms; 1 mcg = 100,000 units (Ref).
Acute myeloid leukemia following induction or consolidation chemotherapy (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 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: 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). However, to minimize possible emergency care needs during the COVID-19 pandemic, it may be reasonable to provide prophylactic WBC growth factors to patients at a lower anticipated neutropenic fever risk (eg, >10%). Telemedicine may be a reasonable option to evaluate if the febrile patient requires a clinic or emergency care environment. Follow standard guidelines for acute care in patients with known neutropenic fever, regardless of COVID-19 status (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 for autologous transplantation in patients with non-Hodgkin lymphoma or multiple myeloma (off-label combination): 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 for up to 8 days (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.
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.
Renal impairment at treatment initiation:
Neupogen 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 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).
(For additional information see "Filgrastim (including biosimilars): Pediatric drug information")
Note: 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).
Refer to adult dosing.
Acute respiratory distress syndrome: Discontinue filgrastim.
Allergic reactions (serious): Permanently discontinue filgrastim.
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
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) [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) [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
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 for autologous transplantation in patients with non-Hodgkin lymphoma or multiple myeloma; 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 eflapegrastim, tbo-filgrastim, pegfilgrastim, sargramostim.
Neupogen may be confused with Epogen, Neulasta, Neumega, 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.
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, hypersensitivity angiitis, vasculitis (aortitis)
Dermatologic: Sweet syndrome
Hematologic & oncologic: Sickle cell crisis, splenic rupture
Hypersensitivity: Anaphylaxis
Neuromuscular & skeletal: Asthenia, decreased bone mineral density, myalgia, osteoporosis
Renal: Glomerulonephritis
Respiratory: Acute respiratory distress syndrome, hemoptysis, 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:
• Allergic reactions: Serious allergic reactions (including anaphylaxis) have been reported, usually with the initial exposure; may be managed symptomatically with administration of antihistamines, steroids, bronchodilators, and/or epinephrine. Allergic reactions may recur within days after the initial allergy management has been stopped.
• Alveolar hemorrhage: Reports of alveolar hemorrhage, manifested as pulmonary infiltrates and hemoptysis (requiring hospitalization), have occurred in healthy donors undergoing peripheral blood progenitor cell mobilization (off-label for use in healthy donors); hemoptysis resolved upon discontinuation.
• Aortitis: Aortitis has been reported in patients receiving filgrastim; aortitis may occur as early as the first week after treatment initiation. Manifestations of aortitis may include generalized fever, abdominal pain, malaise, back pain, and increased inflammatory markers (eg, c-reactive protein, WBC count). Consider aortitis in patients who develop related signs/symptoms of unknown etiology.
• Capillary leak syndrome: Capillary leak syndrome (CLS), characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration, may occur in patients receiving human granulocyte colony-stimulating factors (G-CSF). CLS episodes may vary in frequency and severity. CLS may be life-threatening if treatment is delayed.
• Cutaneous vasculitis: Moderate or severe cutaneous vasculitis has been reported, generally occurring in patients with severe chronic neutropenia on chronic therapy.
• 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; monitor platelet counts.
• Myelodysplastic syndrome: Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have been associated with filgrastim when used in conjunction with chemotherapy and/or radiotherapy in patients with breast and lung cancer. Cytogenetic abnormalities and transformation to MDS and AML have also been observed with filgrastim in patients with severe chronic neutropenia (SCN). Abnormal cytogenetics and MDS are associated with the eventual development of AML. MDS and AML have also occurred in the natural history of SCN without cytokine therapy. Consider the benefits versus risks of continuing filgrastim in patients with SCN who develop abnormal cytogenetics or myelodysplasia (the effects of continuing filgrastim in patients SCN with abnormal cytogenetics or MDS are unknown).
• Nephrotoxicity: Based on findings of azotemia, hematuria (micro- and macroscopic), proteinuria, and renal biopsy, glomerulonephritis has occurred in patients receiving filgrastim. Glomerulonephritis usually resolved after filgrastim dose reduction or discontinuation.
• Respiratory distress syndrome: Acute respiratory distress syndrome (ARDS) has been reported. Evaluate patients who develop fever and lung infiltrates or respiratory distress for ARDS.
• Splenic rupture: Rare cases of splenic rupture have been reported (may be fatal); in patients with upper abdominal pain, left upper quadrant pain, or shoulder tip pain, withhold treatment and evaluate for enlarged spleen or splenic rupture.
Disease-related concerns:
• Severe chronic neutropenia: Establish diagnosis of 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.
• Sickle cell disorders: Severe and sometimes fatal sickle cell crises may occur in patients with sickle cell disorders receiving filgrastim products.
Special populations:
• Older adults: The American Society of Clinical Oncology (ASCO) Recommendations for the Use of WBC Growth Factors Clinical Practice Guideline Update recommend that prophylactic colony-stimulating factors be used in patients ≥65 years of age with diffuse aggressive lymphoma treated with curative chemotherapy (eg, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), especially if patients have comorbid conditions (ASCO [Smith 2015]).
• 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:
• Appropriate use: ASCO guidelines for the use of WBC growth factors state that the prophylactic use of WBC growth factors to reduce the risk of neutropenic fever is reasonable when the anticipated risk of neutropenic fever for the chemotherapy regimen is approximately ≥20% (ASCO [Smith 2015]). Growth factors should not be routinely used in the treatment of established neutropenic fever. CSFs may be considered in cancer patients with febrile neutropenia who are at high risk for infection-associated complications or who have prognostic factors indicative of a poor clinical outcome (eg, prolonged and severe neutropenia, >65 years of age, hypotension, pneumonia, sepsis syndrome, presence of invasive fungal infection, uncontrolled primary disease, hospitalization at the time of fever development) (ASCO [Smith 2006]; IDSA [Freifeld 2011]). CSFs should not be routinely used for patients with neutropenia who are afebrile. Dose-dense regimens that require CSFs should only be used within the context of a clinical trial or if supported by convincing evidence (ASCO [Smith 2015]).
• 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.
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
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. Information related to the use of granulocyte-colony stimulating factor (G-CSF) in pregnant patients with congenital, cyclic, or idiopathic neutropenia (Boxer 2015; Zeidler 2014) and G-CSF-induced allogeneic peripheral blood stem cells donation is limited (Leitner 2001; Shibata 2003).
Data collected from the Severe Chronic Neutropenia International Registry (SCNIR) note dosing for chronic conditions may need adjusted in pregnant women; the lowest effective dose to maintain the absolute neutrophil count is recommended (Zeidler 2014). An international consensus panel has published guidelines for hematologic malignancies during pregnancy that 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) and 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 the 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.
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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.
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 (Releuko Injection)
300 mcg/mL (per mL): $190.80
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
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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