pegfilgrastim (Rx)

>10%

Bone pain (31%)

1-10%

Pain in extremity (9%)

<1%

Leukocytosis (WBC counts >100 x 10^9/L)

Postmarketing Reports

Gastrointestinal disorders: Splenic rupture and splenomegaly, glomerulonephritis

Blood and lymphatic system disorder: Sickle cell crisis, leukocytosis, capillary leak syndrome

Hypersensitivity Reactions: Allergic reactions/hypersensitivity, including anaphylaxis, skin rash, and urticaria, generalized erythema and flushing, cutaneous vasculitis to skin, and subcutaneous tissue disorders

Respiratory, thoracic, and mediastinal disorders: Acute respiratory distress syndrome (ARDS), alveolar hemorrhage

General disorders and administration site conditions: Application site reactions (application site hemorrhage, pain, discomfort, bruise, and erythema)

Skin and subcutaneous tissue disorders: Sweet syndrome (acute febrile neutrophilic dermatosis), cutaneous vasculitis, aortitis

Thrombocytopenia

Contact dermatitis and local skin reactions such as rash, pruritus, and urticaria with on-body injector (possibly indicating a hypersensitivity reaction to adhesive)

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in patients with breast and lung cancer receiving chemotherapy and/or radiotherapy

Contraindications

History of serious allergic reactions to pegfilgrastim or filgrastim

Cautions

Rare cases of splenic rupture may occur; evaluate if patient experiences left upper abdominal and/or shoulder tip pain

ARDS reported; evaluate symptoms, including fever, pulmonary infiltrates, or respiratory distress; discontinue if ARDS occurs

Serious allergic reactions (eg, anaphylaxis) can occur; majority of reported events occurred upon initial exposure; allergic reactions, including anaphylaxis, can recur within days after the discontinuation of initial antiallergic treatment; permanently discontinue treatment in patients with serious allergic reactions (see Contraindications)

Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders; discontinue therapy if sickle cell crisis occurs

Capillary leak syndrome may occur; may vary in frequency and severity; closely monitor patients who develop symptoms and provide standard symptomatic treatment, which may include a need for intensive care

Glomerulonephritis reported; if suspected, evaluate for cause; if causality likely, consider dose reduction or interruption of therapy

Leukocytosis observed; monitoring CBC count during therapy recommended; higher counts reported

Pegfilgrastim may potentially act as growth factor for any tumor type, including myeloid malignancies and myelodysplasia

Missed or partial doses reported in patients receiving drug via OBI due to device not performing as intended; in event of missed or partial dose, patients may be at increased risk of events such as neutropenia, febrile neutropenia and/or infection than if dose had been correctly delivered; instruct patients using OBI to notify their healthcare professional immediately in order to determine need for replacement dose if they suspect that device may not have performed as intended

Aortitis reported; 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 (eg, C-reactive protein and white blood cell count); consider aortitis in patients who develop these signs and symptoms without known etiology; discontinue if aortitis is suspected

Increased hematopoietic activity of bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes; this should be considered when interpreting bone imaging results

Thrombocytopenia reported; monitor platelet counts

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) associated with use of pegfilgrastim 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

Pregnancy

Insufficient data available on use in pregnant women to establish whether there is a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Data from published studies in pregnant women exposed to filgrastim products have not established an association of filgrastim product use during pregnancy with major birth defects, miscarriage, or adverse maternal or fetal outcomes

In animal studies, no evidence of reproductive/developmental toxicity occurred in offspring of pregnant rats that received cumulative doses of pegfilgrastim approximately 10 times recommended human dose (based on body surface area); in pregnant rabbits, increased embryolethality and spontaneous abortions occurred at 4 times the maximum recommended human dose simultaneously with signs of maternal toxicity

Lactation

Unknown whether pegfilgrastim is secreted in human milk

Other recombinant G-CSF products are poorly secreted in breast milk, and G-CSF is not orally absorbed by neonates

Caution should be exercised when administered to a nursing female

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 PEG-conjugated human G-CSF; acts on hematopoietic cells by binding to specific cell surface receptors, thereby stimulating proliferation, differentiation, commitment, and end-cell functional activation

Absorption

AUC (100 mcg/kg): 47.9 mcg·hr/mL (0-5 years); 22 mcg·hr/mL (6-11 years); 29.3 mcg·hr/mL (12-21 years)

Excretion

Neutrophil receptor binding is an important component of the clearance of pegfilgrastim, and serum clearance is directly related to the number of neutrophils and body weight

Patients with higher body weights experienced higher systemic exposure to pegfilgrastim after receiving a dose normalized for body weight

Half-life: 15-80 hr (adults); 30.1 hr (0-5 years); 20.2 hr (6-11 years); 21.2 hr (12-21 years)

SC Administration (Prefilled Syringe)

SC use only

Prior to use‚ allow prefilled syringe to reach room temperature for a minimum of 30 min

Do not administer between 14 days before and 24 hr after administration of cytotoxic chemotherapy

Visually inspect prefilled syringe for particulate matter and discoloration prior to administration, whenever solution and container permit; do not administer if discoloration or particulates are observed

Needle cap contains dry natural rubber (derived from latex); avoid in patients with latex allergies

Patients weighing <45 kg

• Prefilled syringe is not designed to allow for direct administration of doses <0.6 mL (6 mg)
• Syringe does not bear graduation marks; thus, direct administration to patients requiring dosing of <0.6 mL (6 mg) is not recommended owing to the potential for dosing errors

SC Administration (Onpro kit)

A healthcare provider must fill the OBI with Neulasta using prefilled syringe and then apply the OBI to the skin (abdomen or back of arm); use the back of the arm if there is a caregiver available to monitor the status of the OBI for Neulasta

Approximately 27 hr after the OBI for Neulasta is applied to the patient’s skin, Neulasta will be delivered over ~45 min

Initiate the same day as the cytotoxic chemotherapy, as long as the OBI delivers Neulasta no less than 24 hr after administration of cytotoxic chemotherapy

Use only prefilled syringe copackaged in kit; prefilled syringe also contains additional solution to compensate for liquid loss during delivery through the OBI for Neulasta

Do not use the OBI to deliver any other drug product; OBI for Neulasta should be applied to intact, nonirritated skin on the arm or abdomen

Storage

Prefilled syringe

• Refrigerate at 2-8°C (36-46°F) in the carton to protect from light; do not shake
• Discard syringes stored at room temperature for >72 hr
• Avoid freezing; if frozen, thaw in the refrigerator before administration
• Discard syringe if frozen more than once

Onpro kit

• Refrigerate at 2-8°C (36-46°F) until ready to use
• Because OBI for Neulasta is at room temperature during the period of use, Neulasta Onpro kit should not be held at room temperature <12 hr prior to use
• Discard kit if stored at room temperature for >12 hr
• Do not use OBI for Neulasta if its packaging has been previously opened