efbemalenograstim alfa (Rx)

>10%

Nausea (51%)

Anemia (15%)

Thrombocytopenia (12%)

Contraindications

History of serious allergic reactions to granulocyte stimulating factor (eg, efbemalenograstim alfa, pegfilgrastim, filgrastim)

Cautions

Fatal splenic rupture: Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture

Acute respiratory distress syndrome (ARDS): Evaluate patients who develop fever, lung infiltrates, or respiratory distress; discontinue if ARDS confirmed

Serious allergic reactions, including anaphylaxis: Permanently discontinue

Sickle cell crises in patients with sickle cell disorders: Discontinue if sickle cell crisis occurs

Glomerulonephritis: Evaluate and consider dose reduction or interruption if causality is likely

Leukocytosis: WBC counts of 100 × ≥10⁹ /L observed in patients receiving recombinant human granulocyte colony-stimiulating factor (rhG-CSF) products; monitor complete blood count (CBC) count during therapy; discontinue if WBC count exceeds 100 × 10⁹/L

Thrombocytopenia: Monitor platelet counts

Capillary leak syndrome: Monitor symptoms; consider intensive care

Potential for tumor growth

• The G-CSF receptor, through which efbemalenograstim alfa acts, has been found on tumor cell lines
• The possibility exists that efbemalenograstim alfa could act as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which it is not approved

Myelodysplasia and myeloid malignancy

• Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in patients with breast and lung cancer
• Monitor patients with breast and lung cancer using efbemalenograstim alfa in conjunction with chemotherapy and/or radiotherapy for signs and symptoms of MDS/AML

Aortitis

• Aortitis reported in patients receiving rhG-CSF products, occurring as early as the first week after starting therapy
• Manifestations may include generalized signs and symptoms (eg, fever, abdominal pain, malaise, back pain, and increased inflammatory markers [eg, C-reactive protein, WBC count])
• Consider aortitis in patients who develop these signs and symptoms without other known etiology
• Discontinue if aortitis suspected

Nuclear imaging

• Increased hematopoietic activity of bone marrow in response to growth factor therapy associated with transient positive bone imaging changes
• Consider this when interpreting bone imaging results

Pregnancy

Available data regarding use in pregnant females are insufficient to establish drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Published studies data on with exposure to other human G-CSF products have not established an association of G-CSF product use during pregnancy with major birth defects, miscarriage, or adverse maternal or fetal outcomes

Animal studies

• No evidence of reproductive/developmental toxicity occurred in offspring of pregnant rats and rabbits that received cumulative doses of efbemalenograstim alfa ~2.6 and 0.7 times, respectively, the recommended human dose (based on body surface area)

Lactation

Data are unavailable on presence of efbemalenograstim alfa or its metabolite in either human or animal milk, effects on breastfed children, or effects on milk production

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

Colony-stimulating factor that acts on hematopoietic cells by binding to specific cell surface receptors, thereby stimulating proliferation, differentiation, commitment, and end cell functional activation

Absorption

Peak plasma time

• Cycle 1: 36 hr
• Cycle 3: 24-30 hr

Peak plasma concentration

• Cycle 1: 1,085 ng/mL
• Cycle 3: 525 ng/mL

AUC

• Cycle 1: 54,858 hr⋅ng/mL
• Cycle 3: 26,217 hr⋅ng/mL

Distribution

Vd

• Cycle 1: 18.8 L
• Cycle 3: 40.7 L

Metabolism

Expected to be metabolized into small peptides by catabolic pathways

Elimination

Half-life

• Cycle 1: 35.6 hr
• Cycle 3: 36.9 hr

Clearance

• Cycle 1: 0.36 L/hr
• Cycle 3: 0.76 L/hr
• Neutrophil receptor binding is an important component of efbemalenograstim alfa clearance and is directly related to number of neutrophils

SC Preparation

Remove from refrigerator (keep prefilled syringe inside carton) at least 30 minutes before administering, to allow product to reach room temperature

Discard any product left at room temperature >48 hr

Inspect visually for particulate matter and discoloration before administration

Solution should appear clear and colorless; discard if discoloration or particulates observed

Do not administer to patients with latex allergy; product contains natural rubber latex, which may cause allergic reactions; needle cap on prefilled syringe contains natural rubber

Prefilled syringe does not bear graduation marks and is intended only to deliver the entire syringe contents (20 mg/mL) for direct administration

SC Administration

Administer SC by a healthcare professional

Administer injection by pinching skin and holding

Inject into abdomen, back or side of upper arms, or thighs

Rotate injection sites

Do not inject into scar tissue or areas that are reddened, inflamed, or swollen

If injecting into abdomen, avoid a 2-inch diameter circle around navel

Once entire dose has been injected, needle safety device will be triggered, pulling needle automatically from skin, and into barrel; entire needle will be covered by needle guard

Storage

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

Do not shake

Discard syringes stored at room temperature >48 hr

Do not freeze; discard syringe if frozen