eflapegrastim (Rx)

>10%

Fatigue (58%)

Nausea (52%)

Diarrhea (40%)

Bone pain (38%)

Headache (29%)

Pyrexia (28%)

Anemia (25%)

Rash (25%)

Myalgia (22%)

Arthralgia (21%)

Back pain (20%)

Decreased appetite (19%)

Peripheral edema (18%)

Abdominal pain (17%)

Dizziness (16%)

Dyspnea (16%)

Cough (15%)

Thrombocytopenia (14%)

Pain (12%)

Pain in extremity (11%)

Local administration reactions (11%)

1-10%

Flushing (10%)

Contraindications

History of serious allergic reactions to eflapegrastim, pegfilgrastim, or filgrastim products

Cautions

Splenic rupture, including fatal cases, can occur following administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) products; evaluate for enlarged spleen or splenic rupture in patients who report left upper abdominal or shoulder pain after administration

Acute respiratory distress syndrome (ARDS) can occur; evaluate patients who develop fever and lung infiltrates or respiratory distress; discontinue in patients with ARDS

Serious allergic reactions, including anaphylaxis, reported; permanently discontinue if serious allergic reaction occurs; contraindicated with history of serious allergic reaction

Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving rhG-CSF products; discontinue if sickle cell crisis occurs

Leukocytosis reported; monitor complete blood count; discontinue if WBC count ≥100x 10⁹/L occurs

Thrombocytopenia reported; monitor platelet counts

Possibly acts as growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which eflapegrastim is not approved

Increased hematopoietic activity of bone marrow in response to growth factor therapy associated with transient positive bone imaging findings; consider this when interpreting bone imaging results

Capillary leak syndrome

• Capillary leak syndrome reported and characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration
• If symptoms occur, closely monitor and receive standard symptomatic treatment, which may include need for intensive care
• Episodes may become life-threatening if treatment delayed
• Instruct patients to contact emergency services if experiencing swelling or puffiness and urinating less than usual, trouble breathing, abdominal swelling and feeling of fullness, dizziness or feeling faint, or a general feeling of tiredness

Glomerulonephritis

• Glomerulonephritis reported; generally resolves after dose reduction or discontinuation
• If glomerulonephritis suspected, evaluate for cause; if causality likely, consider dose-reduction or interruption
• Instruct patients to contact healthcare provider if experiencing swelling of the face or ankles, blood in urine or dark colored urine, or urinating less than usual

MDS and AML

• Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have been associated with 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
• Instruct patients to contact healthcare professional if experiencing tiredness, fever, and easy bruising or bleeding

Aortitis

• Aortitis may occur as early as first week after initiating
• Manifestations may include generalized signs and symptoms such as fever, abdominal pain, malaise, back pain, and increased inflammatory markers (eg, C-reactive protein, WBC count)
• Discontinue if aortitis suspected
• Instruct patient to contact healthcare provider if experiencing fever, abdominal pain, feeling tired, or back pain

Pregnancy

Data are not available regarding use in pregnant females; however, data from published studies with use of other rhG-CSF products during pregnancy have not identified any drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Animal studies

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

Lactation

Data are not available regarding presence in human milk, effects on breastfed children, or effects on milk production

Endogenous G-CSF is present in human milk; other rhG-CSF products are present in human milk at low levels and are not orally absorbed by infants

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Recombinant human granulocyte growth factor (G-CSF) that binds to G-CSF receptors on myeloid progenitor cells and neutrophils, triggering signaling pathways that control cell differentiation, proliferation, migration, and survival

Absorption

Peak plasma time: 25 hr (range: 6-144 hr)

Distribution

Vd: 1.44 L

Metabolism

Degraded endogenously following stimulation and receptor-mediated internalization

Elimination

Half-life 36.4 hr (range: 16.1-115 hr)

Clearance: Increases with repeat administration, potentially due to increase in neutrophil count

Excretion: Not detected in urine

SC Preparation

Remove carton from refrigerator (keep prefilled syringe inside carton) for minimum of 30 minutes to allow product to reach room temperature

Discard any prefilled syringe left at room temperature >12 hr

Do not shake

Remove tray from box and carefully remove syringe; if dropped onto a hard surface, do not use it; use new syringe for the injection

Clear, colorless solution

Inspected visually for particulate matter and discoloration; discard if discoloration or particulates observed

SC Administration

Administer entire contents of prefilled syringe SC

Prefilled syringe does not bear graduation marks and is intended only to deliver the entire contents of syringe

Administer ~24 hr after cytotoxic chemotherapy; do not administer within the period from 14 days before to 24 hr after administering cytotoxic chemotherapy

Storage

Refrigerate at 36-46ºF (2-8ºC) in carton to protect from light

Do not shake

Discard syringes stored at room temperature for >12 hr

Do not freeze; discard syringe if frozen

Not made with natural rubber latex