Drug class: Hematopoietic Agents

Medically reviewed by Drugs.com on Feb 10, 2024. Written by ASHP.

Introduction

Filgrastim is a biosynthetic (recombinant DNA origin) hematopoietic agent that principally affects the proliferation and differentiation of neutrophils within the bone marrow and possibly other sites (e.g., spleen). 2

Filgrastim and tbo-filgrastim are structurally and pharmacologically similar drugs that contain a related drug substance. Tbo-filgrastim was licensed by the US Food and Drug Administration (FDA) through a biologics license application (BLA), not as a biosimilar to filgrastim.

Filgrastim-sndz, filgrastim-aafi, and filgrastim-ayow are biosimilar to filgrastim (Neupogen). A biosimilar is a biological that is highly similar to an FDA-licensed reference biological with the exception of minor differences in clinically inactive components and for which there are no clinically meaningful differences in safety, purity, or potency. Biosimilars are approved through an abbreviated licensure pathway that establishes biosimilarity between a proposed biological and reference biological but does not independently establish safety and effectiveness of the proposed biological. In order to be considered an interchangeable biosimilar, a biological product must meet additional requirements beyond demonstrating biosimilarity to its reference product. None of the currently available filgrastim biosimilars have interchangeable data at this time.

Uses for Filgrastim

Chemotherapy-induced Neutropenia

• Filgrastim, tbo-filgrastim, and biosimilars: reduces the incidence of infection, as seen by the presence of febrile neutropenia, in patients with non-myeloid malignancies administered myelosuppressive chemotherapeutic agents associated with a clinically significant incidence of febrile neutropenia.

• In adults receiving chemotherapy for a solid tumor or non-myeloid malignancy, guidelines recommend that colony stimulating factors (CSFs) be administered prophylactically when the risk of febrile neutropenia is high (exceeding 20%) and if equally effective treatments that do not require CSF support are unavailable.

• For patients receiving chemotherapy regimens who have an intermediate risk of febrile neutropenia (10–20%), prophylactic use of CSFs can be considered, especially if the increased risk is due to patient factors (e.g., >65 years of age, coexisting illness) instead of the chemotherapy regimen.

• Prophylaxis is generally not recommended for patients with a low risk (<10%) of febrile neutropenia.

Acute Myeloid Leukemia - Induction and/or Consolidation Chemotherapy

• Filgrastim and biosimilars: decreases the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML).

Bone Marrow Transplantation (BMT)

• Filgrastim and biosimilars: decreases the duration of neutropenia and neutropenia-related clinical sequelae in patients with non-myeloid malignancies undergoing myeloablative chemotherapy followed by BMT.

Autologous Peripheral Blood Progenitor Cell Collection and Therapy

• Filgrastim and biosimilars (except filgrastim-ayow): mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis.

Severe Chronic Neutropenia

• Filgrastim and biosimilars: reduces the incidence and duration of sequelae of neutropenia in symptomatic patients with congenital, cyclic, or idiopathic neutropenia.

Acute Exposure to Myelosuppressive Doses of Radiation

• Filgrastim (Neulasta): improves survival in patients acutely exposed to myelosuppressive radiation doses.

Filgrastim Dosage and Administration

General

Pretreatment Screening

• Obtain a complete blood count (CBC) and platelet count at baseline.

• For patients with suspected chronic neutropenia, confirm the diagnosis prior to filgrastim therapy through evaluation of serial CBCs with differential, platelet counts, and bone marrow morphology and karyotype.

Patient Monitoring

• Monitor for signs and symptoms of serious allergic reactions during therapy.

• Monitor platelet counts during therapy; frequency is indication-dependent.

• Monitor CBC during therapy; frequency is indication-dependent.

• Monitor for the development of left upper abdominal or shoulder pain during therapy and evaluate patients who develop these symptoms for splenic enlargement or rupture.

• Monitor for the development of fever and lung infiltrates or respiratory distress during therapy and evaluate patients who develop these signs and symptoms for acute respiratory distress syndrome.

• Monitor for signs and symptoms of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) in patients with breast and lung cancer who use filgrastim products concomitantly with chemotherapy and/or radiotherapy and in patients with severe chronic neutropenia.

• Monitor for the development of sickle cell crisis in patients with sickle cell disorders.

• Monitor kidney function and evaluate for glomerulonephritis if it is suspected.

• Monitor closely for the development of signs and symptoms of capillary leak syndrome during therapy (e.g., hypotension, hypoalbuminemia, edema, hemoconcentration).

• Monitor for signs and symptoms of aortitis (e.g., fever, abdominal pain, malaise, back pain, increased inflammatory markers).

Dispensing and Administration Precautions

• Patients with latex allergies should not receive filgrastim (Neupogen) or filgrastim-sndz (Zarxio) via prefilled syringes as the needle cap contains dry natural rubber.

• The filgrastim biosimilar prefilled syringe formulations do not allow for direct administration of doses <0.3 mL (180 mcg) to patients due to the potential for dosing errors. For doses <0.3 mL, use of the single-dose vial is recommended.

• The Institute for Safe Medication Practices (ISMP) notes that the brand name Neupogen may be potentially confused with the brand name Neumega.

Administration

Administer filgrastim products by sub-Q injection, short IV infusion (15 to 30 minutes), or continuous IV infusion, depending on the product and indication for use. May also be administered by continuous sub-Q infusion^{† [off-label]} .

If given sub-Q, inject into the outer area of the upper arms, abdomen (except for the 2-inch area around the navel), thighs, and the upper outer areas of the buttocks. Rotate injection sites daily; avoid any area that is tender, red, bruised, scaly, hard, or has stretch marks or scars.

If a filgrastim product is administered by a patient or caregiver and a dose is missed, contact the healthcare provider.

Discard any unused portion of filgrastim product in vials or prefilled syringes. Do no re-enter the vial and do not save unused filgrastim product for administration at a later date.

Visually inspect for particulate matter and discoloration prior to administration. Do not administer if particulate matter or discoloration observed. Avoid shaking filgrastim products. Transport of filgrastim via a pneumatic tube system has not been evaluated.

Filgrastim (Neupogen)

Supplied in single-dose prefilled syringes (for sub-Q use) and single-dose vials (for both sub-Q use and IV infusion).

Dilution

If IV administration required, dilute filgrastim (vial only) in 5% Dextrose from a concentration of 300 mcg/mL to 5 mcg/mL. Do not dilute to <5 mcg/mL. Protect filgrastim, diluted to concentrations from 5 to 15 mcg/mL, from adsorption to plastic by adding Albumin (Human) to a final concentration of 2 mg/mL.

Filgrastim diluted in 5% Dextrose or 5% Dextrose plus Albumin (Human) is compatible with glass bottles, polyvinyl chloride and polyolefin IV bags, and polypropylene syringes. Do not dilute with saline as precipitation may occur. Store the diluted solution at room temperature for up to 24 hours, which includes time during storage and the duration of the infusion.

For continuous sub-Q infusion^{† [off-label]}, dilute in 10–50 mL of 5% dextrose injection and infuse at a rate not exceeding 10 mL/24 hours.

Tbo-filgrastim (Granix)

Supplied in single-dose prefilled syringes and vials for sub-Q use.

Filgrastim biosimilars (Zarxio; Nivestym; Releuko)

Supplied in single-dose prefilled syringes for sub-Q use (Zarxio; Nivestym; Releuko) and single-dose vials for sub-Q or IV use (Nivestym; Releuko).

Dilution

If IV administration is required, dilute Nivestym and Releuko (vial only) in 5% Dextrose from a concentration of 300 mcg/mL to 5 mcg/mL. Do not dilute to <5 mcg/mL. Protect these biosimilars, diluted to concentrations from 5 to 15 mcg/mL, from adsorption to plastic by adding Albumin (Human) to a final concentration of 2 mg/mL.

Nivestym and Releukodiluted in 5% Dextrose or 5% Dextrose plus Albumin (Human) are compatible with glass bottles, polyvinyl chloride and polyolefin IV bags, and polypropylene syringes. Do not dilute with saline as precipitation may occur. Store the diluted solution at room temperature for up to 24 hours (Nivesytm) or up to 4 hours (Releuko), which includes time during storage and the duration of the infusion.

Dosage

Chemotherapy-induced Neutropenia

Obtain CBC and platelet count at baseline and monitor twice weekly during therapy.

Administer at least 24 hours after cytotoxic chemotherapy; do not give within 24-hour period prior to chemotherapy.

Filgrastim and biosimilars (filgrastim-sndz, filgrastim-aafi, filgrastim-ayow):

Sub-Q injection, short IV infusion (15 to 30 minutes), or continuous IV infusion: 5 mcg/kg/day. Consider dose increases in increments of 5 mcg/kg for each chemotherapy cycle, based on duration and severity of ANC nadir.

One to 2 days after initiation, transient increase in neutrophil count typically observed. To ensure sustained response, administer for up to 2 weeks or until ANC has reached 10,000 cells/mm³ following expected chemotherapy-induced nadir. Duration of therapy may be dependent on myelosuppressive potential of chemotherapy regimen.

Tbo-filgrastim:

Sub-Q injection: 5 mcg/kg/day. Specifically labelled only for use in adults and pediatric patients ≥1 month of age.

.

Acute Myeloid Leukemia - Induction and/or Consolidation Chemotherapy

Filgrastim and biosimilars (filgrastim-sndz, filgrastim-aafi, filgrastim-ayow):

Sub-Q injection, short IV infusion (15 to 30 minutes), or continuous IV infusion: 5 mcg/kg/day.

Consider dose increases in increments of 5 mcg/kg for each chemotherapy cycle, based on duration and severity of ANC nadir.

Obtain CBC and platelet count at baseline and monitor twice weekly during therapy.

Administer at least 24 hours after cytotoxic chemotherapy; do not give within 24-hour period prior to chemotherapy.

One to 2 days after initiation, transient increase in neutrophil count typically observed. To ensure sustained response, administer for up to 2 weeks or until ANC has reached 10,000 cells/mm³ following expected chemotherapy-induced nadir. Duration of therapy may be dependent on myelosuppressive potential of chemotherapy regimen.

Bone Marrow Transplantation (BMT)

Filgrastim and biosimilars (filgrastim-sndz, filgrastim-aafi, filgrastim-ayow):

IV: 10 mcg/kg/day infusion for no longer than 24 hours. Give initial dose at least 24 hours after cytotoxic chemotherapy and at least 24 hours after bone marrow infusion.

Monitor platelet counts and CBCs frequently after BMT.

During neutrophil recovery, titrate daily dosage against the neutrophil response (See Table 1).

If ANC reduces to <1000 cells/mm³ at any time while the patient is receiving 5 mcg/kg/day, increase the dosage to 10 mcg/kg/day, and then follow the steps in Table 1.

Autologous Peripheral Blood Progenitor Cell Collection and Therapy

Filgrastim and biosimilars (filgrastim-sndz, filgrastim-aafi):

Sub-Q injection: 10 mcg/kg/day.

Give for at least 4 days before initial leukapheresis procedure and continue until last procedure. Optimal duration of administration and leukapheresis schedule not established; administration for 6 to 7 days with leukaphereses on days 5, 6, and 7 has been found to be effective and safe.

Monitor neutrophil counts after 4 days of filgrastim and discontinue if WBC count rises to >100,000 cells/mm³.

Severe Chronic Neutropenia

Filgrastim and biosimilars (filgrastim-sndz, filgrastim-aafi, filgrastim-ayow):

Sub-Q injection: 6 mcg/kg twice daily (congenital neutropenia); 5 mcg/kg once daily (idiopathic or cyclic neutropenia)

Chronic daily therapy required for continued benefit. Individualize dosage based on ANC and clinical course. Lower median daily dosages necessary for patients with idiopathic (1.2 mcg/kg) and cyclic (2.1 mcg/kg) neutropenia as compared to congenital (6 mcg/kg) neutropenia. Rarely, patients with congenital neutropenia may require dosages ≥100 mcg/kg/day.

Monitor CBCs with differential and platelet counts during initial 4 weeks of therapy, during the 2 weeks following any dosage adjustment, and monthly during first year of treatment once patient is clinically stable. If patient remains clinically stable after initial year of treatment, less frequent routine monitoring is recommended.

Acute Exposure to Myelosuppressive Doses of Radiation

Filgrastim (Neupogen):

Sub-Q: 10 mcg/kg as a single daily injection. Give dose as soon as possible after suspected or confirmed exposure to radiation doses >2 gray. Continue until ANC is >1000 cells/mm³ for 3 consecutive CBCs or exceeds 10,000 cells/mm³ after a radiation-induced nadir.

Obtain a baseline CBC and subsequent serial CBCs approximately every third day until ANC is >1000 cells/mm³ for 3 consecutive CBCs. Do not delay therapy if a CBC is not readily available.

Estimate the level of radiation exposure via clinical findings, biodosimetry (if available), and information from public health authorities.

Special Populations

Hepatic Impairment

Manufacturers of filgrastim and the biosimilars state dosage adjustment is not necessary. Manufacturer of tbo-filgrastim makes no specific dosage recommendations.

Renal Impairment

Manufacturers of filgrastim and the biosimilars state dosage adjustment not necessary. Manufacturer of tbo-filgrastim makes no specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions for Filgrastim

Contraindications

• History of serious allergic reactions to human granulocyte colony-stimulating factors such as pegfilgrastim or filgrastim products.

Warnings/Precautions

Splenic Rupture

Splenic rupture, including fatal cases, reported. Monitor patients for left upper abdominal pain or shoulder pain as these may be suggestive of an enlarged spleen or splenic rupture.

Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) reported. Monitor patients for fever and lung infiltrates or respiratory distress as these may be suggestive of ARDS. Discontinue in patients with ARDS.

Serious Allergic Reactions

Serious allergic reactions, including anaphylaxis, reported. Most occur upon initial exposure. Serious allergic reactions, including anaphylaxis, can recur within days after discontinuing treatment for the initial reaction. Permanently discontinue in patients with serious allergic reactions. Do not administer to patients with a history of serious allergic reactions to these products or pegfilgrastim.

Sickle Cell Disorders

Severe sickle cell crises, including fatal cases, reported in patients with sickle cell disorders. Discontinue therapy if a crisis occurs.

Glomerulonephritis

Glomerulonephritis reported with therapy. If suspected, assess for the underlying etiology. If a filgrastim product is the likely cause, consider reducing the dose or interrupting therapy.

Leukocytosis

To avoid risks associated with leukocytosis, discontinue therapy in patients with cancer receiving chemotherapy if ANC >10,000 cells/mm³after the chemotherapy-induced ANC nadir occurs. Monitor CBCs at least twice weekly. Filgrastim dosages that increase the ANC >10,000 cells/mm³ may not result in additional clinical benefit. Discontinuation in these patients usually resulted in a 50% decrease in circulating neutrophils within 1 to 2 days, with a return to baseline in 1 to 7 days.

For patients with cancer undergoing PBPC mobilization, discontinue filgrastim if the leukocyte count increases to >100,000 cells/mm³.

Thrombocytopenia

Thrombocytopenia reported with therapy. Monitor platelet counts.

Capillary Leak Syndrome

Symptoms of capillary leak syndrome (e.g., hypotension, hypoalbuminemia, edema, hemoconcentration) may occur. May be life-threatening if treatment delayed. Closely monitor patients who develop capillary leak syndrome and initiate symptomatic treatment.

Tumor Growth Stimulatory Effects

May potentially act as growth factors for any tumor type. Safety in the setting of chronic myeloid leukemia (CML) and myelodysplasia specifically has not been established.

When used to mobilize PBPC, tumor cells may be collected in the leukapheresis product and subsequently reinfused. Effects of reinfusion of tumor cells not well studied and available data are inconclusive.

Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)

Patients with breast and lung cancer who receive filgrastim products in conjunction with chemotherapy and/or radiotherapy may potentially develop MDS and AML. Monitor for signs and symptoms of MDS/AML.

For patients with severe chronic neutropenia, confirm the diagnosis prior to filgrastim administration. Patients with severe chronic neutropenia who received filgrastim have experienced cytogenetic abnormalities, MDS transformation, and AML. Risk of MDS and AML development appears to be confined to the subset of patients with congenital neutropenia. Unknown what effect filgrastim has on the development of abnormal cytogenetics and the effect that continued administration has in patients with abnormal cytogenetics or MDS. Monitor for signs and symptoms of MDS/AML in these settings. Consider risks and benefits of continued therapy in patients with severe chronic neutropenia who develop abnormal cytogenetics or myelodysplasia.

Aortitis

Signs and symptoms of aortitis (e.g., fever, abdominal pain, malaise, back pain, and increased inflammatory markers) have been reported and may occur as soon as the initial week of treatment. Discontinue if aortitis suspected.

Nuclear Imaging

Transient positive bone imaging changes may occur due to increased hematopoietic bone marrow activity. Consider these changes when interpreting bone imaging results.

Alveolar Hemorrhage and Hemoptysis

Alveolar hemorrhage and hemoptysis necessitating hospitalization reported in patients undergoing PBPC collection mobilization. Discontinuation of therapy resulted in hemoptysis resolution. Use for PBPC mobilization in healthy donors is not an approved use.

Cutaneous Vasculitis

Cutaneous vasculitis reported; severity ranging from moderate to severe. Majority of patients administered long-term therapy for severe chronic neutropenia. If cutaneous vasculitis occurs, hold filgrastim therapy. When symptom resolution occurs and ANC decreases, may reinitiate at a reduced dosage.

Simultaneous Use with Chemotherapy and Radiation Therapy

Safety and efficacy of filgrastim products administered simultaneously with cytotoxic chemotherapy and/or radiotherapy have not been established. Avoid simultaneous use.

Do not use in the period 24 hours before through 24 hours after the administration of cytotoxic chemotherapy.

Immunogenicity

Anti-drug antibodies have been detected with filgrastim product use.

Specific Populations

Pregnancy

No link between filgrastim use during pregnancy and the occurrence of major birth defects, miscarriage, or adverse maternal or fetal outcomes established.

Tbo-filgrastim should be used during pregnancy only if the potential benefit justifies the potential fetal risk.

Lactation

Case reports describe use of filgrastim in breast-feeding mothers; no adverse effects observed in exposed infants. No data exist regarding effects on milk production. Consider benefits of breast-feeding and mother’s need for filgrastim against any potential adverse effects on breast-feeding infant or underlying maternal condition.

No data are available regarding presence of tbo-filgrastim in breastmilk, effects on the breastfed child, or effects on milk production.

Pediatric Use

In a study of patients with cancer administered myelosuppressive chemotherapy, 15 pediatric patients were administered filgrastim doses of 5, 10, or 15 mcg/kg/day for 10 days. Pharmacokinetics of filgrastim in pediatric patients after chemotherapy administration comparable to those seen in adults. Filgrastim also well tolerated with the only consistently reported adverse event being musculoskeletal pain.

Effectiveness and safety of filgrastim in pediatric patients with severe chronic neutropenia also established. A postmarketing surveillance study included 429 pediatric patients with severe chronic neutropenia. Results suggest that height and weight are not adversely affected in patients administered up to 5 years of filgrastim therapy. Limited data do not suggest alterations in sexual maturation or endocrine function as well.

Development of cytogenetic abnormalities and transformation to MDS and AML have occurred in pediatric patients with congenital types of neutropenia given long-term therapy. Relationship between filgrastim administration and these adverse events is unknown.

Administration of filgrastim to increase survival in pediatric patients acutely exposed to myelosuppressive radiation doses based on results from animal studies and clinical data supporting use in other indications.

Tbo-filgrastim is approved for use in pediatric patients >1 month old with non-myeloid malignancies receiving myelosuppressive chemotherapy associated with a clinically significant incidence of febrile neutropenia, to reduce the duration of severe neutropenia. Approval based on evidence from studies in adults and additional safety and pharmacokinetics data from a trial of 50 pediatric patients with solid tumors administered tbo-filgrastim.

Geriatric Use

For patients administered myelosuppressive chemotherapy, no differences in effectiveness or safety observed between older and younger patients.

For other approved indications, insufficient numbers of patients ≥65 years of age to determine whether response was different from younger patients.

In clinical studies of tbo-filgrastim, no differences in effectiveness or safety observed between patients ≥65 years of age and younger patients.

Renal Impairment

Increased filgrastim concentrations noted in patients with end-stage renal disease as compared to healthy subjects and patients with moderate renal impairment. Pharmacokinetics of tbo-filgrastim not studied in patients with moderate or severe renal impairment; mild renal impairment had no effect on tbo-filgrastim pharmacokinetics.

Hepatic Impairment

Pharmacokinetics and pharmacodynamics of filgrastim were comparable between healthy subjects and patients with hepatic impairment (mild to moderate). Pharmacokinetics of tbo-filgrastim not evaluated in hepatic impairment.

Common Adverse Effects

Most common (≥5% difference compared to placebo) adverse reactions in patients with non-myeloid malignancies administered myelosuppressive chemotherapy receiving filgrastim and biosimilars include pyrexia, pain, rash, cough, dyspnea.

Most common (≥2% difference compared to placebo) adverse reactions in patients with AML receiving filgrastim and biosimilars include pain, epistaxis, rash.

Most common (≥5% difference compared to placebo) adverse reaction in patients with non-myeloid malignancies undergoing myeloablative chemotherapy followed by BMT receiving filgrastim and biosimilars includes rash.

Most common (≥5%) adverse reactions in patients undergoing PBPC mobilization and collection receiving filgrastim and biosimilars include bone pain, pyrexia, headache.

Most common (≥5% difference compared to placebo) adverse reactions in patients with severe chronic neutropenia receiving filgrastim and biosimilars include pain, anemia, epistaxis, diarrhea, hypoesthesia, alopecia.

Most common (≥1%) adverse reaction for patients administered tbo-filgrastim is bone pain.

Drug Interactions

No formal drug interaction studies performed.

Filgrastim Pharmacokinetics

Absorption

Exhibits nonlinear pharmacokinetics.

Filgrastim is rapidly absorbed following sub-Q injection. Peak serum concentrations generally are attained within 4–5 hours.

Absolute bioavailability of filgrastim after sub-Q administration: 60–70%.

Median time to peak plasma concentrations of sub-Q tbo-filgrastim in patients with cancer: approximately 4–6 hours. Absolute bioavailability of tbo-filgrastim following sub-Q injection: approximately 33%.

Distribution

Filgrastim is rapidly distributed in animals, appearing in highest concentrations in bone marrow, adrenal glands, kidney, and liver.

Volume of distribution of filgrastim following a single IV or sub-Q dose averages 150 mL/kg (range: 46–384 mL/kg) in both healthy individuals and patients with cancer.

Unknown whether filgrastim is distributed into CSF. Published literature exists documenting filgrastim transfer into human milk. There have been reports of transplacental passage of filgrastim products in pregnant women when administered within 30 hours of preterm delivery.

Elimination

Elimination Route

Eliminated by both renal elimination and specific degradation by G-CSF receptors and neutrophil elastase.

Clearance dependent on filgrastim concentration and neutrophil count; G-CSF receptor-mediated clearance saturated by high concentrations of filgrastim and diminished by neutropenia.

Half-life

Manufacturer states that the elimination half-life of filgrastim following sub-Q or IV administration averages 3.5 hours (range: 0.77–8.5 hours) in healthy individuals or patients with cancer.

Median elimination half-life of tbo-filgrastim in patients with cancer receiving chemotherapy is 3.2–3.8 hours; in healthy individuals, median half-life of the drug was approximately 8.9 hours.

Stability

Storage

Parenteral

Injection

Filgrastim (Neupogen): Store prefilled syringe or vial under refrigeration (2° to 8°C); protect from light. Prior to administration, remove from refrigeration and allow to reach room temperature for at least 30 minutes and no more than 24 hours. Avoid freezing; however, if frozen, thaw in refrigerator prior to administration. Discard any prefilled syringe or vial frozen more than once or left at room temperature for >24 hours.

Tbo-filgrastim (Granix): Store prefilled syringe or vial under refrigeration (2° to 8°C); protect from light. Prior to administration, remove from refrigeration and allow to reach room temperature for at least 30 minutes. May be removed from refrigeration for a single period of up to 5 days between 23° to 27°C and returned to refrigeration, up to product expiration date, if not used during the 5 day period. Exposure to -1° to -5°C for up to 72 hours and temperatures as low as -15° to -25°C for up to 24 hours do not adversely affect stability.

Filgrastim biosimilars (Zarxio; Nivestym; Releuko): Store prefilled syringe or vial under refrigeration (2° to 8°C); protect from light. Prior to administration, remove the Zarxio prefilled syringe from refrigeration and allow to reach room temperature for at least 30 minutes and for a maximum of 4 days. Avoid freezing; however, if frozen, thaw in refrigerator prior to administration. Discard any prefilled syringe frozen more than once or left at room temperature for >4 days. Prior to administration, remove the Nivestym and Releukoprefilled syringe or vial from refrigeration and allow to reach room temperature for at least 30 minutes and no more than 24 hours. Avoid freezing; however, if Nivestym is frozen, thaw in refrigerator prior to administration. Do not freeze Releuko. Discard any prefilled syringe or vial frozen more than once or left at room temperature for >24 hours.

Actions

• Filgrastim, tbo-filgrastim, and biosimilars are hematopoietic agents that principally influence leukopoiesis.

• Appear to elicit the same pharmacologic effects produced by endogenous human granulocyte colony-stimulating factor (G-CSF).

• Endogenous G-CSF, a growth factor, is a lineage-restricted CSF that principally affects the proliferation, differentiation, and activation of committed progenitor cells of the neutrophil-granulocyte lineage.

• In addition, endogenous G-CSF enhances certain functions of mature neutrophils, including phagocytosis, chemotaxis, and antibody-dependent cellular cytotoxicity (ADCC).

Advice to Patients

• Instruct patients who self-administer filgrastim products as to the proper administration and disposal procedures.

• Advise patients of the potential risk of serious allergic reactions. Symptoms may include rash, shortness of breath, wheezing, dizziness, swelling around the mouth or eyes, fast heart rate, and sweating.

• Inform patients of the potential risk for rupture or enlargement of the spleen. Patients should report any pain in the left upper stomach area or left shoulder to their healthcare provider.

• Advise patients of the risk for acute respiratory distress syndrome. Advise patients to contact their healthcare provider if any shortness of breath (with or without a fever), trouble breathing, or fast breathing occurs.

• Inform patients with sickle cell disease to report any symptoms of sickle cell crisis (e.g., pain, difficulty breathing) to their healthcare provider.

• Advise patients of the potential for kidney injury. Advise patients to contact their healthcare provider if any swelling of the face or ankles, blood in the urine or dark colored urine, or urination less frequently than normal occurs.

• Advise patients to report any unusual bleeding or bruising to their healthcare provider.

• Inform patients of the potential risk of capillary leak syndrome. Advise patients to contact emergency medical services if any of the following symptoms occur: trouble breathing, swelling of the stomach area and feeling of fullness, dizziness or feeling faint, swelling or puffiness, a reduction in urination, and a general feeling of tiredness.

• Inform patients of the potential for aortitis (inflammation of the aorta). Advise patients to report any symptoms of aortitis (e.g., fever, abdominal pain, feeling tired, back pain) to their healthcare provider.

• Advise patients with breast or lung cancer of the increased risk of development of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with therapy when used in conjunction with chemotherapy and/or radiotherapy and inform patients with congenital neutropenia who receive filgrastim of this potential increased risk as well. These patients should report any tiredness, fever, and easy bruising or bleeding to their healthcare provider.

• Inform patients of the potential risk of cutaneous vasculitis. Advise patients to report signs or symptoms of vasculitis (e.g., purpura, erythema) to their healthcare provider immediately.

• Inform clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Importance of females informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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Frequently asked questions

• How many biosimilars have been approved in the United States?
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