Introduction
Udenyca (pegfilgrastim-cbqv) is a biosimilar to Neulasta (pegfilgrastim), which is a pegylated form of recombinant human granulocyte colony-stimulating factor (G-CSF). It is a hematopoietic agent specifically developed to reduce the duration of neutropenia and incidence of febrile neutropenia in patients receiving myelosuppressive chemotherapy.
Mechanism of Action
Udenyca works by binding to specific cell surface receptors on hematopoietic cells, stimulating proliferation, differentiation, commitment, and end-cell functional activation. Pegfilgrastim-cbqv is a covalent conjugate of recombinant human G-CSF and monomethoxypolyethylene glycol. The pegylation reduces renal clearance and prolongs the half-life of the drug, allowing for once-per-chemotherapy-cycle dosing.
Indications
Udenyca is FDA-approved for:
- Decreasing the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia
- Increasing survival in patients acutely exposed to myelosuppressive doses of radiation (radiation myelosuppression)
Dosage and Administration
Standard dosing: 6 mg administered subcutaneously once per chemotherapy cycle Timing: Administer approximately 24 hours after completion of chemotherapy Special populations:- No dosage adjustment required for renal or hepatic impairment
- Not recommended for use in pediatric patients under 45 kg
- Elderly patients: No specific dosage adjustment required
Pharmacokinetics
Absorption: Bioavailability is approximately 70% following subcutaneous administration Distribution: Volume of distribution is approximately 150 mL/kg Metabolism: Undergoes minimal metabolism, primarily cleared through neutrophil-mediated elimination Elimination: Half-life is approximately 15-80 hours (significantly longer than filgrastim due to pegylation) Clearance: Primarily through binding to G-CSF receptors on neutrophil precursors and mature neutrophilsContraindications
- History of serious allergic reactions to pegfilgrastim or filgrastim products
- Patients with known hypersensitivity to E. coli-derived proteins
Warnings and Precautions
Splenic rupture: Cases of splenic rupture, including fatal cases, have been reported Acute respiratory distress syndrome: May occur in patients receiving pegfilgrastim products Serious allergic reactions: Anaphylaxis has been reported Sickle cell crises: Serious and sometimes fatal sickle cell crises have occurred Glomerulonephritis: Has been reported; evaluate and consider dose reduction or discontinuation Leukocytosis: White blood cell counts exceeding 100,000/mm³ have been observed Capillary leak syndrome: Has been reported; monitor for symptoms Potential for tumor growth: G-CSF receptors found on tumor cells; possible potential for tumor growthDrug Interactions
- Lithium: May potentiate the release of neutrophils
- Myelosuppressive chemotherapy: Should not be administered within 14 days before and 24 hours after chemotherapy administration
- Other hematopoietic growth factors: Concurrent use not recommended
Adverse Effects
Most common adverse reactions (>10%):- Bone pain
- Pain in extremity
- Splenic rupture
- Acute respiratory distress syndrome
- Allergic reactions
- Sickle cell crisis
- Glomerulonephritis
- Capillary leak syndrome
- Leukocytosis
- Myelodysplastic syndrome and acute myeloid leukemia in patients with breast and lung cancer
Monitoring Parameters
- Complete blood count (CBC) with differential prior to chemotherapy and regularly during treatment
- Monitor for signs and symptoms of splenic rupture (left upper quadrant or shoulder tip pain)
- Respiratory status (for signs of ARDS)
- Renal function
- Signs of allergic reactions
- Symptoms of capillary leak syndrome (hypotension, edema, hypoalbuminemia)
Patient Education
- Inform patients about the potential side effects, particularly bone pain, which is common but usually manageable
- Instruct patients to immediately report left upper quadrant abdominal pain or shoulder tip pain (possible splenic rupture)
- Advise patients to report any signs of allergic reaction (rash, hives, swelling, difficulty breathing)
- Inform patients about the importance of timing the injection (approximately 24 hours after chemotherapy)
- Teach proper subcutaneous injection technique if self-administration is planned
- Advise patients to keep a record of injection dates and any side effects experienced
- Inform patients that white blood cell counts will increase significantly during treatment
References
1. Udenyca® (pegfilgrastim-cbqv) prescribing information. Coherus BioSciences; 2018. 2. Blackwell K, Semiglazov V, Krasnozhon D, et al. Comparison of EP2006, a filgrastim biosimilar, to the reference: a phase III, randomized, double-blind clinical study in the prevention of severe neutropenia in patients with breast cancer receiving chemotherapy. Ann Oncol. 2015;26(9):1948-1953. 3. Aapro MS, Bohlius J, Cameron DA, et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer. 2011;47(1):8-32. 4. Smith TJ, Bohlke K, Lyman GH, et al. Recommendations for the use of WBC growth factors: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2015;33(28):3199-3212. 5. FDA approval letter: Udenyca (pegfilgrastim-cbqv). November 2018.