Eflapegrastim-xnst (Monograph)

Drug class: Hematopoietic Agents

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

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Introduction

Recombinant human granulocyte colony-stimulating factor.

Uses for Eflapegrastim-xnst

Chemotherapy-induced Neutropenia

Eflapegrastim-xnst is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in adult patients with non-myeloid malignancies receiving myelosuppressive chemotherapy associated with clinically significant incidence of febrile neutropenia.

Not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

Current guidelines for use of granulocyte colony-stimulating factors (G-CSFs) in adults with solid tumors or non-myeloid malignancies (e.g., lymphoma) recommend prophylaxis with G-CSFs based upon a patient's risk of developing febrile neutropenia following chemotherapy, taking into account the type of cancer, chemotherapy regimen, patient risk factors, and treatment intent. Prophylaxis recommended for adults with these malignancies who are at high risk of febrile neutropenia (>20%) and can be considered for patients at intermediate risk (10–20%) if risk is due to patient risk factors and not the chemotherapy regimen.

Eflapegrastim-xnst Dosage and Administration

General

Patient Monitoring

Evaluate for enlarged spleen or splenic rupture in patients who report left upper abdominal or shoulder pain after receiving eflapegrastim-xnst.
Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving eflapegrastim-xnst due to concern for acute respiratory distress syndrome.
Monitor CBC, including WBC and platelets, during eflapegrastim-xnst therapy.
Monitor for capillary leak syndrome (i.e., hypotension, hypoalbuminemia, edema, hemoconcentration).
Monitor for signs and symptoms of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in patients with breast and lung cancer.
Monitor for signs and symptoms of aortitis, including fever, abdominal pain, malaise, back pain, and increased inflammatory markers (e.g., C-reactive protein and WBC).

Administration

Administer by sub-Q injection.

Single-dose prefilled syringe; does not have graduation marks. Inspect for particulate matter and discoloration prior to administration; should be a clear, colorless, solution. Do not administer if discoloration or particulates are observed.

Remove from refrigerator and place sealed blister tray on clean, flat surface for minimum of 30 minutes. Do not use if dropped onto a hard surface. Do not shake. Remove from blister tray, gripping syringe by the center of the viewing window; do not remove by the plunger rod, plunger head, or needle cap.

Administer in outer upper arm, abdomen (except 2-inch area around the navel), upper outer buttock, or upper outer thigh. Rotate injection sites; do not administer in same spot used for previous injection. Do not administer in moles, scars, birthmarks, stretch marks, or tender, damaged, bruised, scarred, or hard areas.

May be self-administered. Provide patient or caregiver with Instructions for Use and instruct on proper storage and administration of drug, and safe disposal of syringes and needles.

Dosage

Adults

Chemotherapy-induced Neutropenia

Sub-Q

13.2 mg once per monthly chemotherapy cycle.

Administer approximately 24 hours after chemotherapy. Do not administer within 14 days before to 24 hours after chemotherapy.

Dosage Modification for Toxicity

Reduce dose or interrupt therapy in patients with glomerulonephritis. Discontinue in patients with acute respiratory distress syndrome, suspected aortitis, sickle cell crisis, or if WBC ≥100,000/mm³. Permanently discontinue for severe allergic reactions (including anaphylaxis).

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Patients

No specific dosage recommendations at this time.

Cautions for Eflapegrastim-xnst

Contraindications

History of serious allergic reaction (including anaphylaxis) to eflapegrastim-xnst, pegfilgrastim, or filgrastim.

Warnings/Precautions

Splenic Rupture

Splenic rupture, including fatal cases, can occur. Evaluate for enlarged spleen or splenic rupture in patients who report left upper abdominal or shoulder pain.

Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) can occur. Evaluate patients who develop fever and lung infiltrates or respiratory distress.

Serious Allergic Reactions

Serious allergic reactions, including anaphylaxis, can occur. Permanently discontinue in patients with serious allergic reactions. Contraindicated in patients with a history of serious allergic reaction to eflapegrastim-xnst, pegfilgrastim, or filgrastim.

Sickle Cell Crisis in Patients with Sickle Cell Disorders

Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders. Discontinue if sickle cell crisis occurs.

Glomerulonephritis

Glomerulonephritis has occurred. Generally, events resolved after dose reduction or discontinuation of product. If glomerulonephritis is suspected, evaluate for cause. If causality is likely, continue dose reduction or interruption of eflapegrastim-xnst.

Leukocytosis

WBC counts ≥100,000/m³ have been observed. Monitor CBC during therapy. Discontinue treatment if WBC count ≥100,000/m³ occurs.

Thrombocytopenia

Thrombocytopenia has been reported. Monitor platelet counts.

Capillary Leak Syndrome

Capillary leak syndrome has been reported, characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration. Episodes vary in frequency and severity, and may be life-threatening if treatment delayed. Closely monitor patients who develop symptoms of capillary leak syndrome and administer standard symptomatic treatment, which may include need for intensive care.

Potential for Tumor Growth Stimulatory Effects on Malignant Cells

The G-CSF receptor through which eflapegrastim-xnst acts has been found on tumor cell lines. The possibility that eflapegrastim-xnst acts as a growth factor for any tumor type cannot be excluded.

Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) in Patients with Breast and Lung Cancer

MDS and AML associated with use of rhG-CSF products in conjunction with chemotherapy and/or radiotherapy in patients with breast and lung cancer. Monitor for signs and symptoms of MDS/AML in these settings.

Aortitis

Aortitis has been reported and may occur as early as the first week after the start of therapy. Manifestations may include generalized signs and symptoms such as fever, abdominal pain, malaise, back pain, and increased inflammatory markers (e.g., C-reactive protein and WBC). Consider aortitis in patients who develop these signs and symptoms without known etiology. Discontinue if aortitis is suspected.

Nuclear Imaging

Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging findings. Consider when interpreting bone imaging results.

Immunogenicity

Antibodies to eflapegrastim-xnst detected. There was no clinically significant effect of anti-drug antibodies on pharmacokinetics, pharmacodynamics, safety, or effectiveness of eflapegrastim-xnst over a treatment duration of 12 weeks. There was no identified clinically significant effect of anti-drug antibodies on the safety profile of eflapegrastim-xnst during a 12-month follow-up period after the last dose.

Specific Populations

Pregnancy

No available data on use in pregnant females; however, data from published studies with the use of other rhG-CSF products in pregnant females have not identified any drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

Lactation

No data on the presence of eflapegrastim-xnst in human milk, the effects on the breast-fed child, or the effects on milk production. Endogenous G-CSF is present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for eflapegrastim-xnst and any potential adverse effects on the breast-fed child from eflapegrastim-xnst or from the underlying maternal condition.

Pediatric Use

Safety and efficacy in pediatric patients not established.

Geriatric Use

No overall differences in safety or effectiveness of eflapegrastim-xnst were observed between older and younger patients in clinical studies.

Common Adverse Effects

Most common adverse events (≥20%): fatigue, nausea, diarrhea, bone pain, headache, pyrexia, anemia, rash, myalgia, arthralgia, back pain.

Drug Interactions

Expected to be metabolized by endogenous degradation following receptor-mediated internalization by cells bearing the G-CSF receptor.

No studies evaluating drug interaction potential have been conducted.

Eflapegrastim-xnst Pharmacokinetics

Absorption

Exhibits nonlinear pharmacokinetics. Absolute neutrophil count, C_max, and area under the effect curve (AUEC) increase with increasing doses in a linear, but less than dose-proportional, manner over a dose range of 45 to 350 mcg/kg.

Onset

T_max achieved 25 (range, 6-144) hours after sub-Q injection.

Elimination

Clearance decreases with repeat administration (i.e., cycle 3 compared to cycle 1), suggesting target-mediated clearance by neutrophils.

Metabolism

Endogenous degradation following receptor-mediated internalization by cells bearing the G-CSF receptor.

Elimination

Not detected in the urine.

Half-life

36.4 (range, 16.1-115) hours.

Stability

Storage

Parenteral

Injection, for sub-Q use

Store at 2-8°C in the original container. Discard if left at room temperature >12 hours. Do not freeze.

Actions

rhG-CSF produced by covalent coupling of a human G-CSF analog and an Fc fragment of human immunoglobulin G₄, both derived from recombinant Escherichia coli, via a single polyethylene glycol linker.
Recombinant G-CSF domain is a variant of human G-CSF with two serine substitutions at positions 17 and 65 and no additional N-terminal methionine.
Binds to G-CSF receptors on myeloid progenitor cells and neutrophils, triggering signaling pathways that control cell differentiation, proliferation, migration, and survival.
Elevates neutrophil counts in healthy and cancer patients.

Advice to Patients

Advise patients to read the FDA-approved patient labeling.
For patients that self-administer eflapegrastim-xnst, advise patients on the process for preparation, storage, and correct injection technique. Provide and advise patients of the importance of following the Instructions for Use. Advise patients of the dangers of reusing syringes and the importance of following local requirements for proper disposal of used syringes.
Advise patients of the risk of splenic rupture and splenomegaly. Advise patients to report left upper abdominal or shoulder pain to their clinician.
Advise patients of the risk of acute respiratory distress syndrome. Advise patients to report fever, shortness of breath with or without fever, trouble breathing, or a fast rate of breathing to their clinician.
Advise patients of the risk of serious allergic reactions, including anaphylaxis, which may present as rash, shortness of breath, wheezing, dizziness, swelling around the mouth or eyes, fast heart rate, and sweating. Advise patients that experience these symptoms to contact their clinician or get emergency medical help immediately. Advise patients that they should not receive eflapegrastim-xnst if they have a history of serious allergic reaction to eflapegrastim-xnst, pegfilgrastim, or filgrastim.
Advise patients with sickle cell disorders of the risk of sickle cell crisis. Advise patients that experience symptoms of sickle cell crisis, including pain and difficulty breathing, to contact their clinician immediately.
Advise patients on the risk of glomerulonephritis. Advise patients to report swelling of the face or ankles, blood in the urine or dark colored urine, or decreased urination to their clinician.
Advise patients of the need to monitor white blood cell and platelet counts while receiving eflapegrastim-xnst. Advise patients that unusual bleeding or bruising should be reported to their clinician.
Advise patients on the risk of capillary leak syndrome. Advise patients to obtain emergency medical care if they experience swelling and are urinating less than usual, have trouble breathing, swelling of the abdomen and feeling of fullness, dizziness or feeling faint, or a general feeling of tiredness.
Advise patients with breast and lung cancer of the risk of myelodysplastic syndrome and acute myeloid leukemia when eflapegrastim-xnst is used in conjunction with chemotherapy and/or radiation therapy. Advise patients to report symptoms including tiredness, fever, and easy bruising or bleeding to their clinician.
Advise patients of the risk of aortitis. Advise patients to report symptoms including fever, abdominal pain, malaise, and back pain to their clinician.
Advise patients who are or intend to become pregnant that it is not known whether eflapegrastim-xnst can harm an unborn child. Advise patients that it is unknown whether eflapegrastim-xnst is distributed into breast milk. Advise patients to inform their clinician if they are or intend to become pregnant.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
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.

Eflapegrastim-xnst is obtained through designated specialty distributors and specialty pharmacies. Visit [Web] for specific availability information.