eukocytosis and bone pain. Events of edema, dyspnea, andpleural effusion have been reported in a single patient who administered pegfilgrastim on 8 consecutive days inerror. In the event of overdose, the patient should be monitored for adverse reactions [see Adverse Reactions (6.1)].
11 DESCRIPTION
Pegfilgrastim-cbqv is a covalent conjugate of recombinant methionyl human G-CSF andmonomethoxypolyethylene glycol. Recombinant methionyl human G-CSF is a water-soluble, 175 amino acidprotein with a molecular weight of approximately 19 kilodaltons (kDa). Recombinant methionyl human G-CSF isobtained from the bacterial fermentation of a strain of E coli transformed with a genetically engineered plasmidcontaining the human G-CSF gene. During the pegfilgrastim-cbqv manufacturing process, fermentation is carriedout in nutrient medium containing the antibiotic kanamycin. However, kanamycin is cleared in the manufacturingprocess and is not detectable in the final product. To produce pegfilgrastim-cbqv, a 20 kDamonomethoxypolyethylene glycol molecule is covalently bound to the N-terminal methionyl residue of recombinantmethionyl human G-CSF. The average molecular weight of pegfilgrastim-cbqv is approximately 39 kDa.
UDENYCA (pegfilgrastim-cbqv) injection is supplied in 0.6 mL prefilled syringes for manual subcutaneousinjection. The prefilled syringe does not bear graduation marks and is designed to deliver the entire contents of thesyringe (6 mg/0.6 mL).
Each syringe contains 6 mg pegfilgrastim-cbqv (based on protein weight) in a sterile, clear, colorless, preservativefreesolution (pH 4.0) containing acetate (0.35 mg), polysorbate 20 (0.02 mg), sodium (0.02 mg), and sorbitol (30mg) in Water for Injection, USP.
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action
Pegfilgrastim products are colony-stimulating factors that act on hematopoietic cells by binding to specific cellsurface receptors, thereby stimulating proliferation, differentiation, commitment, and end cell functional activation.
12.2Pharmacodynamics
Animal data and clinical data in humans suggest a correlation between pegfilgrastim products’ exposure and the
12.3Pharmacokinetics
The pharmacokinetics of pegfilgrastim were studied in 379 patients with cancer. The pharmacokinetics of
pegfilgrastim were nonlinear, and clearance decreased with increases in dose. Neutrophil receptor binding is an
important component of the clearance of pegfilgrastim, and serum clearance is directly related to the number of
neutrophils. In addition to numbers of neutrophils, body weight appeared to be a factor. Patients with higher body
weights experienced higher systemic exposure to pegfilgrastim after receiving a dose normalized for body weight. A
large variability in the pharmacokinetics of pegfilgrastim was observed. The half-life of pegfilgrastim ranged from
15 to 80 hours after subcutaneous injection.
Specific Populations
No gender-related differences were observed in the pharmacokinetics of pegfilgrastim, and no differences were
observed in the pharmacokinetics of geriatric patients (≥ 65 years of age) compared with younger patients (< 65
years of age) [see Use in Specific Populations (8.5)].
Renal Impairment
In a study of 30 subjects with varying degrees of renal dysfunction, including end stage renal disease, renal
dysfunction had no effect on the pharmacokinetics of pegfilgrastim.
Pediatric Patients with C |
