Version May 2024
Dosage guidance:
Dosage form information: Fulphila (pegfilgrastim-jmdb), Fylnetra (pegfilgrastim-pbbk), Nyvepria (pegfilgrastim-apgf), Stimufend (pegfilgrastim-fpgk), Udenyca (pegfilgrastim-cbqv), and Ziextenzo (pegfilgrastim-bmez) are approved as biosimilars to Neulasta (pegfilgrastim). In Canada, Fulphila, Lapelga, Nyvepria, and Ziextenzo are approved as biosimilars to Neulasta (pegfilgrastim).
Chemotherapy-induced neutropenia, prevention (non-myeloid malignancies) (Neulasta and pegfilgrastim biosimilars):
Note: WBC growth factors are generally recommended to reduce the risk of neutropenic fever when the anticipated risk of neutropenic fever for a chemotherapy regimen is approximately ≥20% (Ref).
SUBQ: 6 mg once per chemotherapy cycle, beginning at least 24 hours after completion of chemotherapy; Note: The prescribing information recommends not administering in the period between 14 days before and 24 hours after administration of cytotoxic chemotherapy; however, while same-day pegfilgrastim may not be as effective as when administered >24 hours after cytotoxic chemotherapy, there are reports of administering pegfilgrastim on the same day following cytotoxic chemotherapy, particularly when patients are unable to return the following day (Ref).
Hematopoietic radiation injury syndrome, acute (Neulasta, Stimufend, and Udenyca): SUBQ: 6 mg once weekly for 2 doses; administer the first dose as soon as possible after suspected or confirmed radiation exposure >2 gray (Gy); do not delay pegfilgrastim if CBC is not readily available. Administer the second dose 1 week after the first dose.
Hematopoietic support/recovery following autologous transplantation (off-label use): SUBQ: 6 mg as a single dose starting ~24 hours after the completion of peripheral blood cell infusion (Castagna 2010, Gerds 2010); consider filgrastim if ANC >500/mm3 is not achieved by day +19 after transplant (Gerds 2010).
Kidney function impairment prior to treatment initiation: There are no dosage adjustments provided in the manufacturer’s labeling; however, in a pharmacokinetic study, renal dysfunction had no effect on pegfilgrastim pharmacokinetics.
Nephrotoxicity during treatment: Glomerulonephritis: Evaluate if glomerulonephritis is suspected; consider dose reduction or therapy interruption if felt due to pegfilgrastim.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Acute respiratory distress syndrome: Discontinue pegfilgrastim.
Aortitis (suspected): Discontinue pegfilgrastim if aortitis is suspected.
Capillary leak syndrome: Monitor closely and manage symptomatically (may require intensive care).
Hypersensitivity (severe allergic reaction): Permanently discontinue pegfilgrastim.
Sickle cell crisis: Discontinue pegfilgrastim.
Refer to adult dosing.
(For additional information see "Pegfilgrastim (including biosimilars): Pediatric drug information")
Note: Fulphila (pegfilgrastim-jmdb), Fylnetra (pegfilgrastim-pbbk), Nyvepria (pegfilgrastim-apgf), Stimufend (pegfilgrastim-fpgk), Udenyca (pegfilgrastim-cbqv), and Ziextenzo (pegfilgrastim-bmez) are approved as biosimilars to Neulasta (pegfilgrastim); approved uses and ages may vary; see product labeling for additional information. In Canada, Fulphila, Lapelga, Nyvepria, and Ziextenzo are approved as biosimilars to Neulasta (pegfilgrastim); approved uses and ages may vary; see product labeling for additional information.
Chemotherapy-induced neutropenia; prevention: Infants, Children, and Adolescents: Administer once per chemotherapy cycle, beginning at least 24 hours after completion of chemotherapy. Do not administer in the period between 14 days before and 24 hours after administration of cytotoxic chemotherapy. Note: 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). Manufacturer weight-band dosing is comparable to 0.1 mg/kg/dose.
<10 kg: SUBQ: 0.1 mg/kg (0.01 mL/kg).
10 to 20 kg: SUBQ: 1.5 mg (0.15 mL).
21 to 30 kg: SUBQ: 2.5 mg (0.25 mL).
31 to <45 kg: SUBQ: 4 mg (0.4 mL).
≥45 kg: SUBQ: 6 mg (0.6 mL).
Hematopoietic radiation injury syndrome (acute): Infants, Children, and Adolescents: Obtain a baseline CBC prior to administration, but do not delay pegfilgrastim use if a CBC is not readily obtainable. Administer 2 doses; the first dose as soon as possible after suspected or confirmed radiation exposure greater than 2 gray (Gy) and administer the second dose 1 week after the first dose. Note: 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). Manufacturer weight-band dosing is comparable to 0.1 mg/kg/dose.
<10 kg: SUBQ: 0.1 mg/kg (0.01 mL/kg).
10 to 20 kg: SUBQ: 1.5 mg (0.15 mL).
21 to 30 kg: SUBQ: 2.5 mg (0.25 mL).
31 to <45 kg: SUBQ: 4 mg (0.4 mL).
≥45 kg: SUBQ: 6 mg (0.6 mL).
No adjustment necessary.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reaction incidences based on studies including concomitant docetaxel therapy.
>10%: Neuromuscular & skeletal: Ostealgia (31%)
1% to 10%: Neuromuscular & skeletal: Limb pain (9%)
<1%:
Hematologic & oncologic: Leukocytosis
Immunologic: Antibody development
Postmarketing:
Cardiovascular: Capillary leak syndrome, hypersensitivity angiitis, vasculitis (aortitis)
Dermatologic: Sweet’s syndrome
Hematologic & oncologic: Sickle cell crisis, splenic rupture, splenomegaly, thrombocytopenia
Hypersensitivity: Anaphylaxis, severe hypersensitivity reaction
Local: Injection site reaction
Renal: Glomerulonephritis
Respiratory: Acute respiratory distress syndrome, pulmonary alveolar hemorrhage
Hypersensitivity (serious allergic reaction, including anaphylaxis) to pegfilgrastim, filgrastim, or any component of the formulation.
Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to E. coli-derived proteins.
Concerns related to adverse effects:
• Aortitis: Aortitis has been reported in patients receiving pegfilgrastim; aortitis may occur as early as the first week after treatment initiation. Manifestations of aortitis may include generalized fever, abdominal pain, malaise, back pain, and increased inflammatory markers (eg, c-reactive protein, WBC count). Consider aortitis in patients who develop related signs/symptoms of unknown etiology.
• 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 products. CLS episodes vary in frequency and severity. CLS may be life-threatening if treatment is delayed.
• Hematologic effects: Leukocytosis (WBC ≥100,000/mm3) has been reported in patients receiving pegfilgrastim products. Thrombocytopenia has also been reported.
• 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. Skin rash, urticaria, generalized erythema, and flushing have been reported.
• Myelodysplastic syndrome: Myelodysplastic syndrome and acute myeloid leukemia have been associated with pegfilgrastim when used in conjunction with chemotherapy and/or radiotherapy in patients with breast and lung cancer.
• 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.
• 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.
• Splenic rupture: Rare cases of splenic rupture have been reported (some fatal); evaluate for an enlarged spleen or splenic rupture in patients who report left upper abdominal pain or shoulder pain.
Disease-related concerns:
• Sickle cell disease: Severe and sometimes fatal sickle cell crises may occur in patients with sickle cell disorders receiving pegfilgrastim products.
Concurrent drug therapy issues:
• Cytotoxic chemotherapy: Do not use pegfilgrastim products 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.
Special populations:
• 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 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 (ASCO [Smith 2015]). The On-body injector has not been studied for use in pediatrics.
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) may contain latex.
• On-body injector (Neulasta): The On-body injector (OBI) is not recommended for use in patients with acute hematopoietic radiation injury syndrome. Missed or partial doses have been reported; the risk for neutropenia, neutropenic fever, and/or infection is increased if a dose is not correctly delivered. Provide patient training and instruct patients to notify health care provider immediately if OBI malfunctions or did not perform as intended.
Other warnings/precautions:
• Nuclear imaging: Increased bone marrow hematopoietic activity due to colony-stimulating factor use has been associated with transient positive bone-imaging changes; interpret results accordingly.
• Tumor growth factor: The G-CSF receptor through which pegfilgrastim (and filgrastim) work has been located on tumor cell lines. Pegfilgrastim may potentially act as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia (pegfilgrastim is not approved for myeloid malignancies).
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)
Solution Auto-injector, Subcutaneous [preservative free]:
Udenyca: Pegfilgrastim-cbqv 6 mg/0.6 mL (0.6 mL)
Solution Prefilled Syringe, Subcutaneous [preservative free]:
Fulphila: pegfilgrastim-jmdb 6 mg/0.6 mL (0.6 mL)
Fylnetra: Pegfilgrastim-pbbk 6 mg/0.6 mL (0.6 mL)
Nyvepria: pegfilgrastim-apgf 6 mg/0.6 mL (0.6 mL)
Stimufend: Pegfilgrastim-fpgk 6 mg/0.6 mL (0.6 mL)
Udenyca: pegfilgrastim-cbqv 6 mg/0.6 mL (0.6 mL)
Ziextenzo: pegfilgrastim-bmez 6 mg/0.6 mL (0.6 mL)
No
Prefilled Syringe Kit (Neulasta Onpro Subcutaneous)
6 mg/0.6 mL (per 0.6 mL): $7,701.59
Solution Auto-injector (Udenyca Subcutaneous)
6 mg/0.6 mL (per 0.6 mL): $5,010.00
Solution Prefilled Syringe (Fulphila Subcutaneous)
6 mg/0.6 mL (per 0.6 mL): $2,505.00
Solution Prefilled Syringe (Fylnetra Subcutaneous)
6 mg/0.6 mL (per 0.6 mL): $3,000.00
Solution Prefilled Syringe (Neulasta Subcutaneous)
6 mg/0.6 mL (per 0.6 mL): $7,701.59
Solution Prefilled Syringe (Nyvepria Subcutaneous)
6 mg/0.6 mL (per 0.6 mL): $4,710.00
Solution Prefilled Syringe (Stimufend Subcutaneous)
6 mg/0.6 mL (per 0.6 mL): $5,160.30
Solution Prefilled Syringe (Udenyca Subcutaneous)
6 mg/0.6 mL (per 0.6 mL): $5,010.00
Solution Prefilled Syringe (Ziextenzo Subcutaneous)
6 mg/0.6 mL (per 0.6 mL): $4,710.64
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Auto-injector, Subcutaneous:
Lapelga: 6 mg/0.6 mL (0.6 mL)
Solution Prefilled Syringe, Subcutaneous:
Fulphila: 6 mg/0.6 mL (0.6 mL)
Lapelga: 6 mg/0.6 mL (0.6 mL)
Neulasta: 6 mg/0.6 mL (0.6 mL)
Nyvepria: 6 mg/0.6 mL (0.6 mL)
Ziextenzo: 6 mg/0.6 mL (0.6 mL)
SUBQ: Administer SUBQ. Do not use 6 mg fixed dose in infants, children, or adolescents <45 kg (Ref). Pegfilgrastim products are available in prefilled syringes; prefilled, single-dose autoinjectors (Udenyca); or kits for use with the On-body injector (OBI) (Neulasta). 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.
Autoinjector (Udenyca): Allow autoinjector to reach room temperature in carton for 30 minutes prior to injection; do not warm in other ways (eg, microwave, hot water, direct sunlight). Administer at a 90° angle into abdomen (except within 2 inches of navel) or thighs (self-administration) or into back of upper arms or upper outer buttocks (caregiver administration); rotate site with each injection. Press firmly against skin to hear first click, continue holding firmly until the orange indicator stops moving and a second click is heard, after the second click is heard continue to hold in place and count to 5 (once the orange indicator fills the viewing window the injection is complete). Contact healthcare provider immediately if viewing window is not completely filled by the orange indicator or there are more than a few drops of liquid on the injection site; may not have received full dose. Also refer to manufacturer labeling for additional administration instructions. Do not inject into birthmarks, clothing, moles, scars, or areas that are bruised, hard, red, or tender. Do not shake autoinjector.
Manual SUBQ 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 (15 to 30 minutes [Ziextenzo]) prior to injection. Engage/activate needle guard following use to prevent accidental needlesticks.
On-body injector (Neulasta): A health care provider must fill the OBI 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 OBI injection status). The OBI system will deliver pegfilgrastim over ~45 minutes approximately 27 hours after application. The OBI 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 OBI dry for ~3 hours before dose delivery. Do not use additional materials to hold OBI in place; this could dislodge the cannula and result in a missed or incomplete dose. Provide patient training and instruct patients to notify health care provider immediately if OBI malfunctions or did not perform as intended (may require a replacement dose). A missed dose may occur if the OBI 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 OBI to oxygen-rich environments (eg, hyperbaric chambers), MRI, x-ray (including airport x-ray), CT-scan, ultrasound, or radiation treatment (may damage injector system). Keep the OBI at least 4 inches away from electrical equipment, including cell phones, cordless phones, microwaves, and other common appliances (injector may not work properly). The OBI is not recommended for use in patients with acute hematopoietic radiation injury syndrome. The OBI has not been studied in pediatric patients. Refer to prescribing information for further details.
The prefilled syringe provided in the OBI 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 OBI; may result in lower than intended dose. The OBI is only for use with pegfilgrastim; do not use to deliver other medications.
Note: Pegfilgrastim is available in prefilled syringes for manual subcutaneous administration or as a kit for use with the Neulasta On-body injector. Direct administration of doses <6 mg using the prefilled syringe is not recommended because it does not have the necessary graduation marks for accurate measurement of doses other than 6 mg.
SubQ: Manual subcutaneous administration: Infants, Children, and Adolescents: Administer subcutaneously 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.
Hematopoietic radiation injury syndrome, acute (Neulasta, Stimufend, and Udenyca): To increase survival in patients acutely exposed to myelosuppressive doses of radiation.
Prevention of chemotherapy-induced neutropenia (Neulasta and pegfilgrastim biosimilars): 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 products are not indicated for mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplant.
Note: Fulphila (pegfilgrastim-jmdb), Fylnetra (pegfilgrastim-pbbk), Nyvepria (pegfilgrastim-apgf), Stimufend (pegfilgrastim-fpgk), Udenyca (pegfilgrastim-cbqv), and Ziextenzo (pegfilgrastim-bmez) are approved as biosimilars to Neulasta (pegfilgrastim). In Canada, Fulphila, Lapelga, Nyvepria, and Ziextenzo are approved as biosimilars to Neulasta (pegfilgrastim).
Hematopoietic support/recovery following autologous transplantation
Neulasta may be confused with Lunesta, Neupogen, Nuedexta.
Pegfilgrastim may be confused with efbemalenograstim alfa, eflapegrastim, filgrastim, sargramostim, tbo-filgrastim.
Udenyca may be confused with Prolia.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Belotecan: Granulocyte Colony-Stimulating Factors may enhance the neutropenic effect of Belotecan. Management: Do not administer granulocyte colony-stimulating factor (G-CSF) until at least 24 hours after completion of belotecan administration. Monitor neutrophil counts and signs/symptoms of neutropenic fever in patients receiving this combination. Risk D: Consider therapy modification
Betibeglogene Autotemcel: Granulocyte Colony-Stimulating Factors may interact via an unknown mechanism with Betibeglogene Autotemcel. Management: Granulocyte-colony stimulating factor is not recommended for 21 days after betibeglogene autotemcel infusion. Risk X: Avoid combination
Bleomycin: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Bleomycin. Specifically, the risk for pulmonary toxicity may be increased. Management: Avoid use of granulocyte colony-stimulating factors 24 hours before (14 days for pegfilgrastim) and 24 hours after the last dose of bleomycin. Risk D: Consider therapy modification
Exagamglogene Autotemcel: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Exagamglogene Autotemcel. Risk X: Avoid combination
Lovotibeglogene Autotemcel: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Lovotibeglogene Autotemcel. Risk X: Avoid combination
Pegloticase: May diminish the therapeutic effect of PEGylated Drug Products. Risk C: Monitor therapy
Pegvaliase: PEGylated Drug Products may enhance the adverse/toxic effect of Pegvaliase. Specifically, the risk of anaphylaxis or hypersensitivity reactions may be increased. Risk C: Monitor therapy
Tisagenlecleucel: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Tisagenlecleucel. Risk X: Avoid combination
Topotecan: Granulocyte Colony-Stimulating Factors may enhance the adverse/toxic effect of Topotecan. Specifically, the risk for the development of interstitial lung disease may be increased. Granulocyte Colony-Stimulating Factors may enhance the myelosuppressive effect of Topotecan. Management: Avoid use of granulocyte colony-stimulating factors 24 hours before (14 days for pegfilgrastim) and 24 hours after the last dose of topotecan. Additionally, monitor patients closely for the development of interstitial lung disease with this combination. Risk D: Consider therapy modification
Outcome data related to the use of pegfilgrastim for chemotherapy-induced neutropenia during pregnancy are limited (Berends 2021; Cardonick 2012). Consensus panel guidelines for hematologic malignancies during pregnancy suggest that although data are limited, administration of granulocyte growth factors during pregnancy may be acceptable (Lishner 2016).
It is not known if pegfilgrastim is present in breast milk. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother, as well as the mother’s underlying condition.
Chemotherapy-induced neutropenia: CBC with differential (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 for signs of acute respiratory distress syndrome (fever, pulmonary infiltrates, and respiratory distress); evaluate for signs of splenic rupture (left upper abdominal pain, shoulder tip pain, or splenomegaly). Monitor for signs/symptoms of allergic reactions, aortitis (generalized fever, abdominal pain, malaise, back pain, and increased inflammatory markers [eg, c-reactive protein, WBC count]), glomerulonephritis (azotemia, microscopic and macroscopic hematuria, proteinuria; may require renal biopsy), capillary leak syndrome (hypotension, hypoalbuminemia, edema and hemoconcentration; monitor closely if capillary leak syndrome develops), and myelodysplastic syndrome and acute myeloid leukemia. Monitor for sickle cell crisis (in patients with sickle cell anemia).
On-body injector: Monitor for evidence of device malfunction.
Pegfilgrastim stimulates the production, maturation, and activation of neutrophils and activates neutrophils to increase both their migration and cytotoxicity. Pegfilgrastim has a prolonged duration of effect relative to filgrastim and a reduced renal clearance.
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.
Excretion: Primarily through binding to neutrophils.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
