Pegfilgrastim-Cbqv

Introduction Overview

Generic Name

pegfilgrastim-cbqv

Brand Name

Udenyca

Dosage Form

injection, solution

Drug Class

Colony stimulating factors

Pharmacokinetics

Absorption:
Pegfilgrastim-cbqv (Udenyca) is administered subcutaneously, where it undergoes absorption into the systemic circulation. Pharmacokinetic studies in 379 cancer patients demonstrated nonlinear pharmacokinetics, with absorption resulting in measurable serum concentrations typically peaking several hours post-dose. The absorption rate influences the onset of neutrophil recovery. Factors such as injection site, subcutaneous tissue blood flow, and patient body weight may affect absorption kinetics. Clinical trials indicate consistent and reliable absorption following the 6 mg subcutaneous dose, whether administered by manual prefilled syringe, autoinjector, or on-body injector.

Distribution:
Pegfilgrastim-cbqv exhibits a moderate volume of distribution consistent with plasma and extracellular fluid compartments, with a molecular weight of approximately 39 kDa due to PEGylation. The drug binds selectively to granulocyte colony-stimulating factor (G-CSF) receptors expressed on hematopoietic progenitor cells and mature neutrophils. PEGylation enhances systemic retention time by reducing renal filtration and enzymatic degradation. Distribution into tissues is limited due to its size and hydrophilicity, contributing to a limited extravascular distribution.

Metabolism:
Pegfilgrastim-cbqv is degraded by proteolytic enzymes primarily after receptor-mediated internalization by neutrophils and other myeloid cells. The PEG moiety reduces proteolytic degradation, prolonging half-life and therapeutic effect. Unlike small molecule drugs, it is not metabolized by cytochrome P450 enzymes nor extensively processed by the liver. Degradation products are amino acids and small peptides eliminated via normal metabolic pathways.

Elimination:
Elimination occurs predominantly through neutrophil-mediated clearance: pegfilgrastim binding to neutrophil receptors triggers internalization and lysosomal degradation, making neutrophil count a critical determinant of clearance rate. As neutrophil counts recover during therapy, clearance accelerates (auto-regulated kinetics). The elimination half-life ranges from approximately 15 to 80 hours, varying with neutrophil levels. Renal impairment does not significantly affect elimination. Excretion of intact drug via kidneys is minimal due to size. Understanding clearance dynamics is important for appropriate dosing and timing relative to chemotherapy cycles.

Dosage Forms

Available Dosage Forms:
- Injection: 6 mg/0.6 mL in a single-dose prefilled syringe intended for manual subcutaneous use only.
- Injection: 6 mg/0.6 mL in a single-dose prefilled autoinjector designed for adult subcutaneous self-administration.
- Injection: 6 mg/0.6 mL in a single-dose prefilled syringe co-packaged with a sterile on-body injector (OBI) for UDENYCA, which facilitates delayed automated subcutaneous administration.

Dosages for Adults and Adolescents:
- Adults receiving myelosuppressive chemotherapy: 6 mg subcutaneous injection administered once per chemotherapy cycle, typically the day after chemotherapy.
- Adults exposed to myelosuppressive doses of radiation: Two 6 mg subcutaneous doses administered one week apart; the first dose as soon as possible after exposure, second dose one week later.

Specific Patient Populations:
- Pediatric patients <45 kg: Weight-based dosing recommended due to fixed syringe volume. Dosage per body weight is:
- <10 kg: 0.1 mg/kg (0.01 mL/kg)
- 10-20 kg: 1.5 mg (0.15 mL)
- 21-30 kg: 2.5 mg (0.25 mL)
- 31-44 kg: 4 mg (0.4 mL)
- Pediatric patients should not use the fixed 6 mg prefilled autoinjector as the dose is not adjustable.

Administration guidance:
- UDENYCA should not be administered between 14 days before and 24 hours after chemotherapy.
- The on-body injector is not recommended for pediatric patients or patients with acute radiation syndrome.
- Patients using the autoinjector must be adults competent to self-administer.
- Prefilled syringes do not bear graduation marks; thus, care must be taken in dosing pediatric patients requiring <6 mg doses.

Mechanism Of Action

Udenyca (pegfilgrastim-cbqv) is a PEGylated recombinant methionyl human granulocyte colony-stimulating factor (G-CSF) biosimilar designed to stimulate the production and activation of neutrophils. At the molecular level, pegfilgrastim binds with high affinity to the specific G-CSF receptor (G-CSFR), a transmembrane protein expressed predominantly on hematopoietic progenitor cells of the neutrophil lineage. This receptor binding triggers receptor dimerization and activation of intracellular signaling cascades.

Upon receptor engagement, intracellular pathways including the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, phosphatidylinositol 3-kinase (PI3K), and mitogen-activated protein kinase (MAPK) pathways are activated. These signaling events promote the proliferation, differentiation, and survival of neutrophil progenitor cells within the bone marrow. Additionally, enhanced maturation and functional activation of mature neutrophils occur, improving their capacity for chemotaxis, phagocytosis, and microbial killing.

The PEGylation of pegfilgrastim prolongs its systemic half-life by reducing renal clearance and proteolytic degradation through steric hindrance. This modification allows for sustained stimulation of neutrophil production over extended periods, reducing the frequency of dosing compared to filgrastim. Clinically, the resultant increase in circulating neutrophils reduces the duration and severity of chemotherapy-induced neutropenia, thereby decreasing the risk of febrile neutropenia and associated infections.

Compared to similar agents such as filgrastim, pegfilgrastim offers a more convenient once-per-cycle dosing due to extended half-life and auto-regulated clearance linked to neutrophil count. Clinical studies have demonstrated equivalency in efficacy and safety profiles between Udenyca and reference pegfilgrastim products, confirming its mechanism as a biosimilar agent with no clinically meaningful differences in function.

Pharmacological Actions

Stimulates proliferation and differentiation of neutrophil progenitor cells in bone marrow.
Enhances maturation and functional activation of mature neutrophils, improving host defense.
Binds specifically to granulocyte colony-stimulating factor (G-CSF) receptor on hematopoietic cells.
Induces intracellular signaling pathways including JAK-STAT, PI3K, and MAPK to promote myeloid cell development.
Prolonged duration of activity due to PEGylation which decreases renal clearance and enzymatic degradation.
Auto-regulated clearance linked to neutrophil counts to prevent excess neutrophilia.
Facilitates recovery from chemotherapy-induced neutropenia and reduces incidence of febrile neutropenia.
Used to stimulate bone marrow recovery after radiation-induced myelosuppression.
Exhibits pharmacokinetic and pharmacodynamic profiles similar to reference pegfilgrastim products.
Reduces risk of infection-related morbidity and hospitalization in patients receiving myelosuppressive chemotherapy.

Therapeutic Or Clinical Uses

Reduction of febrile neutropenia incidence in patients with non-myeloid malignancies undergoing myelosuppressive chemotherapy.
Enhancement of neutrophil recovery following chemotherapy-induced myelosuppression.
Improvement of infection-related outcomes and survival in patients receiving myelosuppressive anti-cancer drugs.
Increase in survival for patients acutely exposed to myelosuppressive doses of radiation (hematopoietic acute radiation syndrome).
Supportive care for pediatric patients with chemotherapy-induced neutropenia using weight-based dosing.
Prevention of infection-related complications during cancer treatment with clinically significant neutropenia risk.
Not indicated for mobilization of hematopoietic stem cells for transplantation.
Alternative to reference pegfilgrastim biosimilars offering equivalent clinical efficacy.
Used post-chemotherapy to reduce duration and severity of neutropenia, thus aiding chemotherapy dose intensity maintenance.
Facilitates management of neutropenia in various solid tumor malignancies such as breast cancer and sarcomas.

Side Or Adverse Effects

Bone pain – most common adverse effect, presenting as pain in bones, arms, and legs.
Pain in extremities – musculoskeletal discomfort affecting limbs.
Splenic rupture or splenomegaly – rare, can be fatal; patients presenting with left upper abdominal or shoulder pain must be evaluated urgently.
Acute respiratory distress syndrome (ARDS) – severe pulmonary complication requiring drug discontinuation.
Serious allergic reactions including anaphylaxis – manifesting as rash, wheezing, swelling, dizziness, and hypotension.
Sickle cell crisis – severe vaso-occlusive episodes occurring in patients with sickle cell disorders.
Glomerulonephritis – characterized by kidney injury signs such as hematuria, proteinuria, and azotemia.
Leukocytosis – markedly elevated white blood cell counts (WBC > 100 x 10^9/L) documented but often asymptomatic.
Thrombocytopenia – decreased platelet counts leading to bleeding or bruising tendencies.
Capillary leak syndrome – characterized by hypotension, edema, hypoalbuminemia and potential life-threatening complications.
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) risk when used with chemotherapy/radiotherapy in breast and lung cancer patients.
Injection site and application site reactions – including hemorrhage, pain, discomfort, bruising, erythema, and contact dermatitis especially with on-body injector adhesive.
Sweet's syndrome and cutaneous vasculitis – inflammatory skin reactions reported post administration.
Aortitis – inflammation of the aorta presenting with fever, abdominal and back pain, and increased inflammatory markers.
Alveolar hemorrhage reported in postmarketing surveillance.

Precautions

Avoid administering Udenyca within 14 days before and 24 hours after cytotoxic chemotherapy to reduce adverse effects.
Use caution in patients with sickle cell disorders due to risk of fatal sickle cell crises.
Monitor for splenic enlargement or rupture if patients report left upper quadrant or shoulder pain.
Closely observe for signs of serious allergic reactions and discontinue permanently if they occur.
Consider glomerulonephritis if renal impairment symptoms arise; dose adjustment or interruption may be necessary.
Regular monitoring of complete blood counts is recommended to detect leukocytosis and thrombocytopenia.
Assess for symptoms suggestive of capillary leak syndrome and initiate supportive treatment promptly.
Patients with breast or lung cancer receiving chemotherapy and/or radiotherapy should be monitored for MDS and AML.
Advise patients with a history of severe skin reactions to acrylic adhesives on risks related to on-body injector use.
Avoid use of the on-body injector in patients with Hematopoietic Subsyndrome of Acute Radiation Syndrome and pediatric patients under 45 kg.
Proper patient and caregiver training in administration techniques to ensure accurate dosing.
Advise against reusing syringes and emphasize proper disposal to avoid contamination and injury.
Ensure patients understand how to monitor on-body injector device for proper operation and detect malfunctions.
Advise avoidance of exposure of on-body injector to MRI, CT scans, radiation therapy, and strong electromagnetic fields.
Recommended to keep on-body injector at least 4 inches from electrical devices to prevent interference.

Warnings

Fatal splenic rupture has been reported; evaluate immediately if left upper abdominal or shoulder pain occurs.
Acute respiratory distress syndrome (ARDS) may develop; discontinue Udenyca if ARDS occurs.
Serious allergic reactions including anaphylaxis can occur even upon initial exposure; permanent discontinuation required if reaction occurs.
The on-body injector utilizes acrylic adhesives; patients allergic to acrylics may experience severe skin reactions.
Discontinue therapy if sickle cell crisis occurs due to potential fatal outcomes.
Monitor for and manage signs of glomerulonephritis promptly to prevent renal damage.
Leukocytosis, characterized by high white blood cell counts, may occur and requires monitoring.
Thrombocytopenia may develop; watch for unusual bleeding or bruising.
Capillary leak syndrome is potentially life-threatening; immediate medical attention is necessary if symptoms develop.
Potential tumor growth stimulatory effects cannot be excluded; use cautiously in patients with myeloid malignancies.
Increased incidence of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) may occur in certain cancer patients using combined therapy.
Device failures with on-body injector resulting in missed or partial doses increase risks of neutropenia and infection.
Aortitis, a serious vascular inflammation, has been reported; consider differential diagnosis in febrile patients with abdominal/back pain.
Avoid MRI, CT scan, radiation, and hyperbaric oxygen exposure during on-body injector use due to risk of device failure and injury.
Advise patients not to reapply or reuse an on-body injector removed before completion of dosing.

Contraindication

History of serious allergic or anaphylactic reactions to pegfilgrastim products or filgrastim products.
Known hypersensitivity to any component of Udenyca formulation.
Do not administer with medications for peripheral blood progenitor cell mobilization for stem cell transplantation.
On-body injector contraindicated in patients with history of severe skin reactions to acrylic adhesives.
Pediatric patients weighing less than 45 kg should not use fixed-dose prefilled autoinjector due to dosing inaccuracy.
Avoid Udenyca administration within 14 days before and 24 hours after cytotoxic chemotherapy due to increased toxicity.
Do not use Udenyca ONBODY injector if packaging is opened or damaged or if device shows malfunction signs.
Contraindicated in patients with known hypersensitivity to polyethylene glycol (PEG) or formulation excipients.
Avoid use in patients with untreated or active myeloid leukemias due to potential tumor stimulation.
Known severe renal impairment requires careful consideration despite pharmacokinetic data showing no dose adjustment is needed.

Drug Interactions

Concurrent use with cytotoxic chemotherapy agents requires careful timing; Udenyca should not be administered between 14 days before and 24 hours after chemotherapy.
Potential interactions with drugs affecting neutrophil counts may alter Udenyca efficacy or safety, though no direct pharmacokinetic interactions are established.
No significant metabolism via cytochrome P450 pathways reduces risk of common drug interactions.
Immunosuppressive agents may compound neutropenia risk; consultation recommended.
Concomitant medications causing bone marrow suppression may require close monitoring of blood counts.
No known direct interaction with anticoagulants, but thrombocytopenia monitoring advised during combined use.
Administration with other colony-stimulating factors is not recommended due to additive effects.
Medications inducing immunogenic responses could interfere with pegfilgrastim action or increase hypersensitivity risk.
Avoid co-administration with other injectable biologics through the same site to prevent local reactions.
Interactions with radiopharmaceuticals or diagnostic agents not reported but caution with nuclear imaging due to altered bone marrow activity.
No significant interactions reported with common supportive therapies such as antiemetics or analgesics.
No established interactions affecting absorption or bioavailability owing to parenteral route.
Potential electromagnetic interference affecting on-body injector delivery necessitates caution with certain electronic devices.
Adverse effect profile may be altered with concurrent use of immunomodulators; clinical vigilance advised.
Stable co-administration with antibiotics used for febrile neutropenia treatment has been documented.

Preparations Of The Drug

Prefilled syringe for manual subcutaneous injection: 6 mg pegfilgrastim-cbqv in 0.6 mL clear, colorless, preservative-free solution.
Prefilled single-dose autoinjector designed for adult subcutaneous self-administration delivering 6 mg in 0.6 mL solution.
Single-dose prefilled syringe co-packaged with on-body injector (OBI) delivering 6 mg in 0.6 mL; syringe contains 0.67 mL to compensate delivery loss.
Formulated with inactive ingredients including acetate buffer, polysorbate 20, sodium, and sorbitol in water for injection at pH 4.0.
Drug is sterile and preservative-free, ensuring suitability for injection use.
Prefilled syringes and autoinjectors are supplied with 29-gauge, 1/2 inch UltraSafe Passive™ Needle Guards to minimize needle-stick injury risk.
Packaging is designed to protect from light and must be refrigerated at 2°C to 8°C; do not freeze.
Stored in single-dose cartons optimized for pharmacy dispensing and patient handling.
UDENYCA ONBODY kit includes a prefilled syringe and sterile on-body injector device with instructions for healthcare providers.
Prefilled syringes do not bear graduation marks and are intended to deliver the full contents only; not designed for dose fractionation.
Specialized packaging and labeling ensure differentiation between manual injection and on-body delivery systems.
Prefilled autoinjector and on-body injector devices are single-use, disposable forms designed for convenience and patient compliance.
Additional patient and healthcare provider instructions are provided with each preparation to ensure proper use and handling.
Various NDCs correspond to each preparation form for identification and inventory control.