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Pegfilgrastim

Pronunciation

(peg fil GRA stim)

Index Terms

  • G-CSF (PEG Conjugate)
  • Granulocyte Colony Stimulating Factor (PEG Conjugate)
  • Neulasta Onpro kit
  • Pegylated G-CSF
  • SD/01

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Prefilled Syringe Kit, Subcutaneous [preservative free]:

Neulasta Onpro: 6 mg/0.6 mL (0.6 mL)

Solution, Subcutaneous [preservative free]:

Neulasta: 6 mg/0.6 mL (0.6 mL)

Brand Names: U.S.

  • Neulasta
  • Neulasta Onpro

Pharmacologic Category

  • Colony Stimulating Factor
  • Hematopoietic Agent

Pharmacology

Stimulates the production, maturation, and activation of neutrophils, pegfilgrastim activates neutrophils to increase both their migration and cytotoxicity. Pegfilgrastim has a prolonged duration of effect relative to filgrastim and a reduced renal clearance.

Excretion

Primarily through binding to neutrophils

Half-Life Elimination

SubQ: Pediatrics (100 mcg/kg dose): 0 to 5 years: 30.1 ± 38.2 hours; 6 to 11 years: 20.2 ± 11.3 hours; 12 years and older: 21.2 ± 16 hours; Adults: 15 to 80 hours. Pharmacokinetics (in adults) were comparable between manual subcutaneous injection and the On-body injector system.

Use: Labeled Indications

US labeling:

Prevention of chemotherapy-induced neutropenia: To decrease the incidence of infection (as manifested by febrile neutropenia), in patients with nonmyeloid malignancies receiving myelosuppressive cancer chemotherapy associated with a clinically significant incidence of febrile neutropenia.

Limitation of use: Pegfilgrastim is not indicated for mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplant.

Hematopoietic radiation injury syndrome (acute): To increase survival in patients acutely exposed to myelosuppressive doses of radiation.

Canadian labeling:

Prevention of chemotherapy-induced neutropenia: To decrease the incidence of infection (as manifested by febrile neutropenia), in adult patients with nonmyeloid malignancies receiving myelosuppressive cancer chemotherapy.

Contraindications

Hypersensitivity (serious allergic reaction) to pegfilgrastim, filgrastim, or any component of the formulation

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to E. coli-derived proteins.

Dosing: Adult

Prevention of chemotherapy-induced neutropenia: SubQ: 6 mg once per chemotherapy cycle, beginning at least 24 hours after completion of chemotherapy; Note: Do not administer in the period between 14 days before and 24 hours after administration of cytotoxic chemotherapy.

Hematopoietic radiation injury syndrome (acute): SubQ: 6 mg once weekly for 2 doses. Obtain a baseline CBC prior to administration, but do not delay pegfilgrastim use if a CBC is not readily obtainable. Administer the first dose as soon as possible after suspected or confirmed radiation exposure greater than 2 gray (Gy). Administer the second dose 1 week after the first dose.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Prevention of chemotherapy-induced neutropenia: Note: Do not administer in the period between 14 days before and 24 hours after administration of cytotoxic chemotherapy.

Children and Adolescents <45 kg: SubQ: Administer once per chemotherapy cycle, beginning at least 24 hours after completion of chemotherapy (dose and volume are based on patient weight). Maximum dose: 6 mg (Andre 2007; Borinstein 2009). Note: The prefilled syringe is not designed to allow for direct administration of doses less than 6 mg (0.6 mL). Due to the potential for dosing errors, the manufacturer does not recommend direct administration of doses less than 6 mg (0.6 mL); use caution to avoid dosing errors.

Patients <10 kg: 0.1 mg/kg (0.01 mL/kg volume)

Patients 10 to 20 kg: 1.5 mg (0.15 mL volume)

Patients 21 to 30 kg: 2.5 mg (0.25 mL volume)

Patients 31 to 44 kg: 4 mg (0.4 mL volume)

Children and Adolescents ≥45 kg: SubQ: 6 mg once per chemotherapy cycle, beginning at least 24 hours after completion of chemotherapy

Hematopoietic radiation injury syndrome (acute): Obtain a baseline CBC prior to administration, but do not delay pegfilgrastim use if a CBC is not readily obtainable. Administer the first dose as soon as possible after suspected or confirmed radiation exposure greater than 2 gray (Gy). Administer the second dose 1 week after the first dose.

Children and Adolescents <45 kg: SubQ: Administer 2 doses of pegfilgrastim one week apart (dose and volume are based on patient weight).

Patients <10 kg: 0.1 mg/kg (0.01 mL/kg volume)

Patients 10 to 20 kg: 1.5 mg (0.15 mL volume)

Patients 21 to 30 kg: 2.5 mg (0.25 mL volume)

Patients 31 to 44 kg: 4 mg (0.4 mL volume)

Children and Adolescents ≥45 kg: SubQ: 6 mg once weekly for 2 doses (the second dose should be administered 1 week after the first dose).

Dosing: Renal Impairment

No dosage adjustment necessary.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Reconstitution

Subcutaneous administration from the prefilled syringe: For doses of 6 mg, the prefilled syringe may be used. Direct administration of doses <6 mg using the prefilled syringe is not recommended by the manufacturer (it does not have graduation marks necessary for accurate measurement of doses other than 6 mg).

On-body injector: A health care provider must fill the On-body injector prior to applying to the patient's skin. The On-body delivery system may be applied on the same day as chemotherapy administration as long as pegfilgrastim is delivered no less than 24 hours after chemotherapy is administered.

The prefilled syringe provided in the On-body kit contains overfill to compensate for loss during delivery; do not use for manual subcutaneous injection (will result in higher than recommended dose). Do not use prefilled syringe intended for manual injection to fill the On-body injector; may result in lower than intended dose. The On-body injector has not been studied for use in pediatrics.

Administration

Administer subcutaneously. Do not use 6 mg fixed dose in infants, children, or adolescents <45 kg (Smith 2006). Pegfilgrastim is available in prefilled syringes for manual subcutaneous administration or as a kit for use with the On-body injector. Direct administration of doses <6 mg using the prefilled syringe is not recommended by the manufacturer (it does not have graduation marks necessary for accurate measurement of doses other than 6 mg); use caution to avoid dosing errors.

Manual subcutaneous administration: Administer to outer upper arms, abdomen (except within 2 inches of navel), front middle thigh, or upper outer buttocks. Allow prefilled syringe to reach room temperature for at least 30 minutes prior to injection. Engage/activate needle guard following use to prevent accidental needlesticks

On-body injector: A health care provider must fill the On-body injector prior to applying to the patient’s skin. Apply to intact, nonirritated skin on the back of the arm or abdomen (only use the back of the arm if caregiver is available to monitor On-body injection status). The On-body injector system will deliver pegfilgrastim over ~45 minutes approximately 27 hours after application. The On-body delivery system may be applied on the same day as chemotherapy administration as long as pegfilgrastim is delivered at least 24 hours after chemotherapy is administered. Keep the On-body injector dry for ~3 hours before dose delivery. A missed dose may occur if the On-body injector fails or leaks; if a dose is missed, administer a new dose by manual subcutaneous injection as soon as possible after discovery of missed dose. Do not expose the On-body injector to oxygen-rich environments (eg, hyperbaric chambers), MRI, x-ray (including airport x-ray), CT-scan, or ultrasound (may damage injector system). Keep the On-body injector at least 4 inches away from electrical equipment, including cell phones, cordless phones, microwaves, and other common appliances (injector may not work properly). The On-body injector is not recommended for use in patients with acute hematopoietic radiation injury syndrome. The On-body injector has not been studied in pediatric patients. Refer to prescribing information for further details.

The prefilled syringe provided in the On-body kit contains overfill to compensate for loss during delivery; do not use for manual subcutaneous injection (will result in higher than recommended dose). Do not use prefilled syringe intended for manual injection to fill the On-body injector; may result in lower than intended dose. The On-body injector is only for use with pegfilgrastim; do not use to deliver other medications.

Storage

Store under refrigeration at 2°C to 8°C (36°F to 46°F); do not freeze. If syringe for manual injection is inadvertently frozen, allow to thaw in refrigerator; discard if frozen more than one time. Protect from light. Do not shake. Allow prefilled syringe to reach room temperature for at least 30 minutes prior to injection; discard if kept at room temperature for longer than 48 hours. The On-body injector kit should not be held at room temperature for longer than 12 hours prior to use (discard if stored at room temperature for >12 hours).

Drug Interactions

Belotecan: Granulocyte Colony-Stimulating Factors may enhance the neutropenic effect of Belotecan. Consider therapy modification

Pegloticase: May diminish the therapeutic effect of Pegfilgrastim. Monitor therapy

Topotecan: Granulocyte Colony-Stimulating Factors may enhance the myelosuppressive effect of Topotecan. Consider therapy modification

Test Interactions

May interfere with bone imaging studies; increased hematopoietic activity of the bone marrow may appear as transient positive bone imaging changes

Adverse Reactions

Neuromuscular & skeletal: Ostealgia (31%), limb pain (9%)

<1% (Limited to important or life-threatening): Acute respiratory distress syndrome (ARDS), anaphylaxis, antibody development, capillary leak syndrome, glomerulonephritis, hypersensitivity angiitis, hypertonia, increased serum alkaline phosphatase, increased uric acid, leukocytosis, periorbital edema, peripheral edema, polyarthralgia, polymyalgia rheumatic, severe sickle cell crisis, splenic rupture, splenomegaly, Sweet syndrome

Warnings/Precautions

Concerns related to adverse effects:

• Capillary leak syndrome: Capillary leak syndrome (CLS), characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration, may occur in patients receiving human granulocyte colony-stimulating factors (G-CSF), including pegfilgrastim. CLS episodes vary in frequency and severity. If CLS develops, monitor closely and manage symptomatically (may require intensive care). CLS may be life-threatening if treatment is delayed.

• Hypersensitivity: Hypersensitivity, including serious allergic reactions or anaphylaxis may occur, usually with the initial dose; may recur within days after discontinuation of initial antiallergic treatment. Permanently discontinue for severe reactions. Do not administer in patients with a history of serious allergic reaction to pegfilgrastim or filgrastim. Skin rash, urticaria, generalized erythema, and flushing have been reported.

• Nephrotoxicity: Glomerulonephritis has occurred, and generally resolved after pegfilgrastim dose reduction or discontinuation. Diagnosis was made by the presence of azotemia, microscopic and macroscopic hematuria, proteinuria, and renal biopsy. Evaluate if glomerulonephritis is suspected; if felt due to pegfilgrastim, consider dose reduction or therapy interruption.

• Hematologic effects: Leukocytosis (WBC ≥100,000/mm3) has been reported in patients receiving pegfilgrastim. Monitor complete blood counts during therapy.

• Respiratory distress syndrome: Acute respiratory distress syndrome (ARDS) has been reported with use; evaluate patients with pulmonary symptoms such as fever, pulmonary infiltrates, or respiratory distress for ARDS. Discontinue pegfilgrastim if ARDS occurs.

• Splenic rupture: Rare cases of splenic rupture have been reported (some fatal); patients must be instructed to report left upper abdominal pain or shoulder pain.

Disease-related concerns:

• Sickle cell disease: May precipitate sickle cell crises in patients with sickle cell disorders (severe and sometimes fatal sickle cell crises have occurred with filgrastim).

Concurrent drug therapy issues:

• Cytotoxic chemotherapy: Do not use pegfilgrastim in the period 14 days before to 24 hours after administration of cytotoxic chemotherapy because of the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy. Safety and efficacy have not been established with dose-dense chemotherapy regimens (Smith 2006).

Special populations:

• Elderly patients: The American Society of Clinical Oncology (ASCO) Recommendations for the Use of WBC Growth Factors Clinical Practice Guideline Update recommend that prophylactic colony-stimulating factors be used in patients ≥65 years with diffuse aggressive lymphoma treated with curative chemotherapy (eg, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), especially if patients have comorbid conditions (Smith 2015).

• Pediatric patients: The 6 mg fixed dose should not be used in infants, children, and adolescents weighing <45 kg. Colony-stimulating factor (CSF) use in pediatric patients is typically directed by clinical pediatric protocols. The American Society of Clinical Oncology (ASCO) Recommendations for the Use of WBC Growth Factors Clinical Practice Guideline Update states that CSFs may be reasonable as primary prophylaxis in pediatric patients when chemotherapy regimens with a high likelihood of febrile neutropenia are employed. Likewise, secondary CSF prophylaxis should be limited to high-risk patients. In pediatric cancers in which dose-intense chemotherapy (with a survival benefit) is used, CSFs should be given to facilitate chemotherapy administration. CSFs should not be used in the pediatric population for non-relapsed acute lymphoblastic or myeloid leukemia when no infection is present (Smith 2015). The On-body injector has not been studied for use in pediatrics.

• Stem cell mobilization: Not indicated for peripheral blood progenitor cell (PBPC) mobilization for hematopoietic stem cell transplantation.

Dosage form specific issues:

• Acrylic: Some products may contain acrylic adhesive; patients sensitive to acrylic adhesives may experience a significant reaction.

• Latex: The packaging (needle cover) contains latex.

• On-body injector: The On-body injector is not recommended for use in patients with acute hematopoietic radiation injury syndrome. The On-body injector contains an acrylic adhesive; may result in a significant reaction in patients who react to acrylic adhesives. A health care provider must fill the On-body injector prior to applying to the patient's skin. The On-body delivery system may be applied on the same day as chemotherapy administration as long as pegfilgrastim is delivered no less than 24 hours after chemotherapy is administered. The prefilled syringe provided in the On-body kit contains overfill to compensate for loss during delivery; do not use for manual subcutaneous injection (will result in higher than recommended dose). Do not use prefilled syringe intended for manual injection to fill the On-body injector; may result in lower than intended dose. The On-body injector is only for use with pegfilgrastim; do not use to deliver other medications. Do not expose the On-body injector to oxygen-rich environments (eg, hyperbaric chambers); MRI; x-ray (including airport x-ray); CT scan; or ultrasound (may damage injector system). Keep the On-body injector at least 4 inches away from electrical equipment, including cell phones, cordless phones, microwaves, and other common appliances (injector may not work properly).

Other warnings/precautions:

• Appropriate use: Colony-stimulating factors may be considered in cancer patients with febrile neutropenia who are at high risk for infection-associated complications or who have prognostic factors indicative of a poor clinical outcome (eg, prolonged and severe neutropenia, age >65 years, hypotension, pneumonia, sepsis syndrome, presence of invasive fungal infection, uncontrolled primary disease, hospitalization at the time of fever development) (Freifeld 2011; Smith 2006). Colony-stimulating factors should not be routinely used for patients with neutropenia who are afebrile. Dose-dense regimens that require colony-stimulating factors should only be used within the context of a clinical trial or if supported by convincing evidence. The safety/efficacy of pegfilgrastim in the setting of dose-dense therapy has not been fully established (Smith 2015).

• Tumor growth factor: The granulocyte-colony stimulating factor (G-CSF) receptor through which pegfilgrastim (and filgrastim) work has been located on tumor cell lines. May potentially act as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia (pegfilgrastim is not approved for myeloid malignancies).

Monitoring Parameters

Chemotherapy-induced neutropenia: Complete blood count (with differential) and platelet count should be obtained prior to chemotherapy and as clinically necessary.

Hematopoietic radiation injury syndrome: CBC at baseline (do not delay administration if CBC not readily available); estimate absorbed radiation dose.

Evaluate fever, pulmonary infiltrates, and respiratory distress; evaluate for left upper abdominal pain, shoulder tip pain, or splenomegaly. Monitor for signs/symptoms of glomerulonephritis (azotemia, hematuria, proteinuria) and capillary leak syndrome (hypotension, hypoalbuminemia, edema and hemoconcentration). Monitor for sickle cell crisis (in patients with sickle cell anemia).

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies.

Women who are exposed to Neulasta during pregnancy are encouraged to enroll in the Amgen Pregnancy Surveillance Program (800-772-6436).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience bone pain, injection site pain or irritation, or muscle pain. Have patient report immediately to prescriber signs of capillary leak syndrome (abnormal heartbeat; angina; shortness of breath; weight gain; vomiting blood or vomit that looks like coffee grounds; black, tarry, or bloody stools; urinary retention or change in amount of urine passed; hematuria), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of enlarged or ruptured spleen (left upper abdominal pain or left shoulder pain), dark urine, tachycardia, abnormal heartbeat, dizziness, passing out, sweating a lot, shortness of breath, edema, fast breathing, severe loss of strength and energy, or severe injection site edema, lump, or bruising (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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