Eflapegrastim (Monograph)

Brand name: Rolvedon
Drug class: Hematopoietic Agents

Introduction

Eflapegrastim-xnst is a leukocyte growth factor.

Uses for Eflapegrastim

Eflapegrastim-xnst has the following uses:

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

Eflapegrastim-xnst is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

Eflapegrastim Dosage and Administration

General

Eflapegrastim-xnst is available in the following dosage form(s) and strength(s):

Injection: 13.2 mg/0.6 mL solution in a single-dose prefilled syringe for subcutaneous use.

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

• Recommended dose: 13.2 mg administered subcutaneously once per chemotherapy cycle.

• Administer approximately 24 hours after cytotoxic chemotherapy. Do not administer within the period from 14 days before to 24 hours after administration of cytotoxic chemotherapy.

Related/similar drugs

Neulasta, filgrastim, Zarxio, Neupogen, Udenyca, Granix

Cautions for Eflapegrastim

Contraindications

• Patients with a history of serious allergic reactions to human granulocyte colony-stimulating factors such as eflapegrastim, pegfilgrastim or filgrastim products.

Warnings/Precautions

Splenic Rupture

Splenic rupture, including fatal cases, can occur following the administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) products, such as eflapegrastim-xnst. Evaluate for an enlarged spleen or splenic rupture in patients who report left upper abdominal or shoulder pain after receiving eflapegrastim-xnst.

Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) can occur in patients receiving rhG-CSF products, such as eflapegrastim-xnst. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving eflapegrastim-xnst for ARDS. Discontinue eflapegrastim-xnst in patients with ARDS.

Serious Allergic Reactions

Serious allergic reactions, including anaphylaxis, can occur in patients receiving rhG-CSF products, such as eflapegrastim-xnst. Permanently discontinue eflapegrastim-xnst in patients with serious allergic reactions. Eflapegrastim-xnst is contraindicated in patients with a history of serious allergic reactions to eflapegrastim, pegfilgrastim, or filgrastim products.

Sickle Cell Crisis in Patients with Sickle Cell Disorders

Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving rhG-CSF products, such as eflapegrastim-xnst. Discontinue eflapegrastim-xnst if sickle cell crisis occurs.

Glomerulonephritis

Glomerulonephritis has occurred in patients receiving rhG-CSF products. The diagnoses were based upon azotemia, hematuria (microscopic and macroscopic), proteinuria, and renal biopsy. Generally, events of glomerulonephritis resolved after dose-reduction or discontinuation of rhG-CSF. If glomerulonephritis is suspected, evaluate for cause. If causality is likely, consider dose-reduction or interruption of eflapegrastim-xnst.

Leukocytosis

White blood cell (WBC) counts of 100 × 10⁹/L or greater have been observed in patients receiving rhG-CSF products. Monitor complete blood count (CBC) during eflapegrastim-xnst therapy. Discontinue eflapegrastim-xnst treatment if WBC count of 100 × 10⁹/L or greater occurs.

Thrombocytopenia

Thrombocytopenia has been reported in patients receiving rhG-CSF products. Monitor platelet counts.

Capillary Leak Syndrome

Capillary leak syndrome has been reported after administration of rhG-CSF products and is characterized by hypotension, hypoalbuminemia, edema and hemoconcentration. Episodes vary in frequency and severity, and may be life-threatening if treatment is delayed. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care.

Potential for Tumor Growth Stimulatory Effects on Malignant Cells

The granulocyte colony-stimulating factor (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, including myeloid malignancies and myelodysplasia, diseases for which eflapegrastim-xnst is not approved, cannot be excluded.

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

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

Aortitis

Aortitis has been reported in patients receiving rhG-CSF products. It may occur as early as the first week after 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 white blood cell count). Consider aortitis in patients who develop these signs and symptoms without known etiology. Discontinue eflapegrastim-xnst 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. This should be considered when interpreting bone imaging results.

Specific Populations

Pregnancy

There are no available data on eflapegrastim-xnst use in pregnant women; however, data from published studies with use of other recombinant human granulocyte colony-stimulating factor (rhG-CSF) products in pregnant women have not identified any drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

Animal reproduction studies were conducted in rats and rabbits. In rats, eflapegrastim-xnst did not adversely affect embryofetal and/or postnatal development when administered from organogenesis throughout lactation at doses that produced maternal exposures up to 7 times the exposure at the recommended clinical dose. In rabbits, eflapegrastim-xnst caused embryofetal lethality and reduced fetal weight when administered during the organogenesis period at approximately 6 times the exposure at the clinical dose.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.

In an embryofetal developmental study in rabbits, eflapegrastim-xnst was administered subcutaneously every other day during the period of organogenesis at doses up to 10 times the clinical exposure at the maximum recommended dose of 13.2 mg. Increased post-implantation loss, reduced number of live fetuses, and reduced fetal body weights were observed at 6 times the clinical exposure, based on AUC. No malformations were observed up to 10 times the clinical exposure, based on AUC.

In an embryofetal developmental study in rats, eflapegrastim-xnst administered subcutaneously every other day during the period of organogenesis did not adversely affect embryofetal development at doses up to 7 times clinical exposure, based on AUC.

In a pre- and post-natal development study in rats, eflapegrastim-xnst administered subcutaneously once weekly from organogenesis through lactation did not adversely affect behavioral, developmental, or reproductive parameters at doses up to 7 times the clinical exposure, based on AUC.

Lactation

There are no data on the presence of eflapegrastim-xnst in human milk, the effects on the breastfed child, or the effects on milk production. Endogenous granulocyte colony-stimulating factor (G-CSF) is present in human milk. Other recombinant human granulocyte colony-stimulating factor (rhG-CSF) products are present in human milk at low levels and are not orally absorbed by infants. 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 breastfed child from eflapegrastim-xnst or from the underlying maternal condition.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Of the 314 patients in clinical studies of eflapegrastim-xnst, 39% were 65 and over, while 6% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.

Common Adverse Effects

The most common adverse reactions (≥20%) are fatigue, nausea, diarrhea, bone pain, headache, pyrexia, anemia, rash, myalgia, arthralgia, and back pain.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

Eflapegrastim-xnst is a recombinant human granulocyte growth factor that binds to G-CSF receptors on myeloid progenitor cells and neutrophils, triggering signaling pathways that control cell differentiation, proliferation, migration and survival.

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling (patient information). Eflapegrastim-xnst should only be given by a healthcare professional. Inform patients to contact their healthcare provider with any questions.

• Advise patients of the known risks and potential risks with eflapegrastim-xnst including splenic rupture and splenomegaly, acute respiratory distress syndrome, serious allergic reactions, sickle cell crisis, glomerulonephritis, leukocytosis, thrombocytopenia, capillary leak syndrome, potential for tumor growth stimulatory effects on malignant cells, increased risk of myelodysplastic syndrome and/or acute myeloid leukemia in patients with breast and lung cancer who receive eflapegrastim-xnst in conjunction with chemotherapy and/or radiation therapy, and aortitis.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

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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