In clinical studies, leukocytosis (WBC counts > 100 x 109
/L) was observed in less than 1% of 932 patients with
non-myeloid malignancies receiving pegfilgrastim. No complications attributable to leukocytosis were reported in
clinical studies.
6.2 Immunogenicity
As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation ishighly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody(including neutralizing antibody) positivity in an assay may be influenced by several factors including assaymethodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.
Forthese reasons, comparison of the incidence of antibodies in the studies described below with the incidence ofantibodies in other studies or to other pegfilgrastim products may be misleading.
Binding antibodies to pegfilgrastim were detected using a BIAcore assay. The approximate limit of detection for thisassay is 500 ng/mL. Pre-existing binding antibodies were detected in approximately 6% (51/849) of patients withmetastatic breast cancer. Four of 521 pegfilgrastim-treated subjects who were negative at baseline developed
binding antibodies to pegfilgrastim following treatment. None of these 4 patients had evidence of neutralizingantibodies detected using a cell-based bioassay.
6.3 Postmarketing Experience
The following adverse reactions have been identified during post approval use of pegfilgrastim products. Becausethese reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliablyestimate their frequency or establish a causal relationship to drug exposure.
• Splenic rupture and splenomegaly (enlarged spleen) [see Warnings and Precautions (5.1)]
• Acute respiratory distress syndrome (ARDS) [see Warnings and Precautions (5.2)]
• Allergic reactions/hypersensitivity, including anaphylaxis, skin rash, urticaria, generalized erythema and
flushing [see Warnings and Precautions (5.3)]
• Sickle cell crisis [see Warnings and Precautions (5.4)]
• Glomerulonephritis [see Warnings and Precautions (5.5)]
• Leukocytosis [see Warnings and Precautions (5.6)]
• Capillary leak syndrome [see Warnings and Precautions (5.7)]
• Injection site reactions
• Sweet’s syndrome (acute febrile neutrophilic dermatosis), cutaneous vasculitis
• Aortitis [see Warnings and Precautions (5.9)]
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Although available data with UDENYCA or pegfilgrastim product use in pregnant women are insufficient toestablish whether there is a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetaloutcomes, there are available data from published studies in pregnant women exposed to filgrastim products. These
studies have not established an association of filgrastim product use during pregnancy with major birth defects,miscarriage, or adverse maternal or fetal outcomes.
In animal studies, no evidence of reproductive/developmental toxicity occurred in the offspring of pregnant rats thatreceived cumulative doses of pegfilgrastim approximately 10 times the recommended human dose (based on bodysurface area). In pregnant rabbits, increas |
