Pegneufil6 mg/0.6 ml

Pegneufil is a long-acting, pegylated recombinant human granulocyte colony-stimulating factor (G-CSF) used to help the bone marrow recover from the effects of certain cancer chemotherapy.

• Established, FDA-approved use: To decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies who are receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. Pegneufil is given once per chemotherapy cycle, not daily.
• Established, FDA-approved use (Hematopoietic Syndrome of Acute Radiation Syndrome, H-ARS): To increase survival in adult and pediatric patients acutely exposed to myelosuppressive doses of radiation (approved based on animal efficacy data, as human efficacy trials are not ethical or feasible for this indication).
• Not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

Pegneufil must only be prescribed and administered under the supervision of a qualified physician, typically an oncologist or hematologist, as part of a defined chemotherapy or radiation-exposure treatment plan.

Each single-dose prefilled syringe of Pegfilgrastim [Pegylated Filgrastim] contains 6 mg of pegfilgrastim in 0.6 mL (10 mg/mL) sterile solution for subcutaneous injection. It also contains excipients such as acetate, polysorbate 20, sodium, and water for injection, with the solution buffered to an appropriate pH. It is a clear, colorless, preservative-free solution supplied ready to use; no dilution or reconstitution is required.

Pegneufil is a covalent conjugate of recombinant human granulocyte colony-stimulating factor (filgrastim) and a single 20 kDa polyethylene glycol (PEG) molecule. This pegylation reduces renal clearance of the molecule, so that its clearance from the body is instead governed mainly by neutrophil-receptor-mediated uptake, giving Pegneufil a much longer duration of action than unmodified filgrastim. This allows a single subcutaneous injection to provide neutrophil support for an entire chemotherapy cycle, instead of the daily injections required with short-acting G-CSF products.

Pegneufil is dispensed only against a specialist prescription and is administered as part of a supervised cancer-treatment or radiation-injury treatment plan, with regular blood count monitoring.

Pegneufil belongs to the class of colony-stimulating factors (hematopoietic growth factors), specifically a long-acting (pegylated) recombinant human granulocyte colony-stimulating factor (G-CSF) analog.

Mechanism of Action

Pegfilgrastim [Pegylated Filgrastim] binds to and activates the G-CSF receptor on neutrophil precursor cells in the bone marrow, stimulating their proliferation, differentiation, and maturation into functional neutrophils, and enhancing the survival and function (chemotaxis, phagocytosis) of mature neutrophils. This helps shorten the duration and severity of chemotherapy-induced neutropenia and reduces the risk of febrile neutropenia and associated infections.

Pharmacokinetics

• Absorption: Well absorbed after subcutaneous injection; peak serum concentrations are typically reached within 16-120 hours.
• Distribution: Distributes mainly within the vascular space and bone marrow compartment.
• Metabolism/Clearance: Because of its large pegylated size, renal filtration is minimal; clearance is primarily neutrophil-mediated (self-regulating) — clearance increases as the neutrophil count recovers, providing a built-in feedback mechanism that limits the duration of drug exposure once neutrophil recovery occurs.
• Elimination half-life: Highly variable, approximately 15-80 hours, and inversely related to neutrophil count.

• Pegneufil is given as a subcutaneous (under-the-skin) injection into the abdomen (except a 2-inch area around the navel), the front of the thighs, the outer area of the upper arms, or the upper outer buttocks.
• Allow the prefilled syringe to warm to room temperature for about 30 minutes before injecting; do not warm it any other way (e.g. hot water, microwave).
• Do not shake the syringe.
• Each syringe is for single use only; discard any unused portion — do not re-use or share syringes.
• The first dose in a chemotherapy cycle should be given approximately 24 hours after chemotherapy is completed; it must not be given within 14 days before the next chemotherapy cycle.
• May be administered by a healthcare professional, or by the patient/caregiver at home after proper training on injection technique and safe disposal of sharps.

Lithium

Lithium may potentiate the neutrophil-releasing effects of Pegneufil. Although no formal interaction studies have been conducted, patients receiving both drugs together should have more frequent monitoring of neutrophil counts.

Chemotherapy and Radiotherapy Timing

Pegneufil should not be given in the period from 14 days before to 24 hours after cytotoxic chemotherapy (see Dosage and Administration), because of the potential for increased sensitivity of rapidly dividing myeloid cells to myelosuppressive chemotherapy. The safety and efficacy of Pegneufil given concurrently with chemotherapy and radiation therapy have not been established.

Other Interactions

No clinically significant drug-metabolism (e.g. cytochrome P450) interactions have been identified, as Pegneufil is a protein-based biologic and is not metabolized through hepatic enzyme pathways. Always inform your physician of all medicines being taken.

Very Common

• Bone pain and pain in the extremities — the most frequently reported adverse reactions
• Injection-site reactions (redness, swelling, pain)
• Headache, fatigue, generalized weakness
• Nausea

Common

• Leukocytosis (transient rise in white blood cell count, usually not clinically significant)
• Arthralgia (joint pain), myalgia (muscle pain)

Less Common but Serious

• Splenic rupture — rare but potentially fatal; presents with left upper abdominal or shoulder-tip pain (see Precautions)
• Acute respiratory distress syndrome (ARDS)
• Serious allergic reactions, including anaphylaxis
• Sickle cell crisis in patients with sickle cell disorders, which can be severe or fatal
• Glomerulonephritis
• Capillary leak syndrome — can be life-threatening if not promptly treated
• Cutaneous vasculitis and, rarely, large-vessel vasculitis/aortitis
• Thrombocytopenia
• Rarely, myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) in patients with breast or lung cancer who received Pegneufil with chemotherapy and/or radiotherapy

Patients should seek prompt medical attention for left upper abdominal or shoulder pain, breathing difficulty, signs of allergic reaction, or severe pain crisis while on Pegneufil (see Precautions and Warnings).

Pregnancy

Data on the use of Pegneufil in pregnant women are limited. Animal reproduction studies have shown increased embryolethality at higher doses. Pegneufil should be used during pregnancy only if clearly needed and if the potential benefit to the mother justifies the potential risk to the fetus; use only under the guidance of the treating physician.

Lactation

It is not known whether Pegneufil is excreted in human breast milk. Because many drugs are excreted in human milk and the effects on a nursing infant are unknown, caution should be exercised, and breastfeeding should only continue during treatment if advised appropriate by the treating physician.

• Splenic rupture: Fatal cases have been reported. Evaluate patients who report left upper abdominal pain or shoulder-tip pain for an enlarged spleen or splenic rupture.
• Acute respiratory distress syndrome (ARDS): Evaluate patients who develop fever, lung infiltrates, or respiratory distress; discontinue Pegneufil if ARDS is confirmed and provide appropriate medical management.
• Serious allergic reactions, including anaphylaxis: Most reactions occur on initial exposure. Permanently discontinue Pegneufil in patients with serious allergic reactions and treat appropriately; do not re-administer to patients with a history of such reactions.
• Sickle cell crises: Can occur in patients with sickle cell disorders and may be severe or fatal. Use only with caution in these patients, with adequate hydration, and discontinue if a crisis occurs.
• Glomerulonephritis: Has been reported; if causality is suspected, consider dose reduction or interruption.
• Capillary leak syndrome: Can be life-threatening; characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration. Monitor closely and manage promptly with standard supportive care, including possible intensive care.
• Potential for tumor growth factor effect on myeloid malignancies: The G-CSF receptor is present on some myeloid tumor cell lines; a possibility that Pegneufil could act as a growth factor for such malignancies cannot be excluded. Use with caution in patients with a history of myelodysplastic syndrome, chronic myeloid leukemia, or acute myeloid leukemia.
• Dosing window around chemotherapy: Do not administer in the period from 14 days before to 24 hours after cytotoxic chemotherapy, due to potential increased sensitivity of rapidly dividing myeloid cells (see Dosage and Administration).
• Large-vessel vasculitis/aortitis: Has been reported, sometimes as early as the first week after administration, with symptoms such as fever, abdominal pain, back pain, and elevated inflammatory markers.
• Leukocytosis: Monitor complete blood counts regularly during treatment.
• Specialist supervision required: Pegneufil must be prescribed and administered only under medical supervision, with periodic monitoring of complete blood counts; it should never be self-adjusted or shared with others.

There is limited clinical experience with Pegneufil overdose. Doses higher than recommended have been associated with marked leukocytosis and elevated white blood cell counts, and, based on the drug's pharmacology, bone/musculoskeletal pain may be more pronounced. There is no specific antidote for Pegneufil overdose.

If an overdose is suspected, seek immediate medical attention or contact a poison control center/emergency services right away. Management is supportive, with monitoring of complete blood counts, under medical supervision.

Store in a refrigerator at 2°C to 8°C (36°F to 46°F). Protect from light and do not freeze; discard if accidentally frozen. Before injecting, allow the syringe to reach room temperature for about 30 minutes (do not warm it artificially); if left at room temperature, discard after 48 hours. Do not shake. Keep out of reach of children.

Renal Impairment

No dose adjustment is required in patients with renal impairment, including those with end-stage renal disease, as clearance of Pegneufil is primarily neutrophil-mediated rather than renal.

Hepatic Impairment

No specific dose adjustment recommendations exist, as Pegneufil is not hepatically metabolized; however, formal studies in hepatic impairment are limited.

Elderly Patients

Clinical studies did not identify overall differences in safety or effectiveness between elderly and younger adult patients, but data in patients over 65 years are limited; use with appropriate monitoring.

Pediatric Patients

Safety and efficacy have been established for chemotherapy-induced neutropenia in pediatric patients weighing 10 kg or more, using the weight-based dosing shown in Dosage and Administration. Safety and efficacy have not been established in pediatric patients weighing less than 10 kg.

Pegneufil is given as a single subcutaneous injection once per chemotherapy cycle (approximately every 2-3 weeks, depending on the chemotherapy regimen), for as many cycles as the chemotherapy is continued, as determined by the treating oncologist. For acute radiation exposure, treatment consists of only two doses given one week apart. Treatment duration and repeat dosing should never be adjusted without the prescribing physician's guidance.

Pegfilgrastim [Pegylated Filgrastim] is classified as a colony-stimulating factor, specifically a pegylated recombinant human granulocyte colony-stimulating factor (G-CSF) analog, used as a hematopoietic (blood-cell-supporting) agent.

Pegfilgrastim [Pegylated Filgrastim] is formed by covalently attaching a 20 kDa polyethylene glycol (PEG) molecule to filgrastim (recombinant human G-CSF). It binds to the G-CSF receptor on neutrophil precursors in the bone marrow, stimulating their proliferation, differentiation, and release into the circulation as mature, functional neutrophils, and enhances neutrophil survival and effector functions such as chemotaxis and phagocytosis. Pegylation markedly reduces renal clearance, so that clearance instead depends mainly on neutrophil-receptor-mediated uptake — a self-regulating mechanism whereby clearance increases as neutrophil counts recover. This gives Pegfilgrastim [Pegylated Filgrastim] a prolonged duration of action, allowing a single injection to provide neutrophil support across an entire chemotherapy cycle.

C

Pegneufil is approved for chemotherapy-induced neutropenia in pediatric patients weighing 10 kg or more, using weight-tiered dosing (see Dosage and Administration): 1.5 mg for 10 to <21 kg, 2.5 mg for 21 to <31 kg, 4 mg for 31 to <45 kg, and the full 6 mg adult dose for ≥45 kg. Safety and efficacy have not been established in pediatric patients weighing less than 10 kg, and Pegneufil should be used in children only under the direct supervision of a pediatric oncologist.