NURSING MOTHERS SECTION.

8.2 Lactation. Risk SummaryThere are no data on the presence of pegfilgrastim products in human milk, the effects on the breastfed child, or the effects on milk production. Other filgrastim products are secreted poorly into breast milk, and filgrastim products are not orally absorbed by neonates. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for UDENYCA and any potential adverse effects on the breastfed child from UDENYCA or from the underlying maternal condition.

OVERDOSAGE SECTION.

10 OVERDOSAGE. Overdosage of pegfilgrastim products may result in leukocytosis and bone pain. Events of edema, dyspnea, and pleural effusion have been reported in single patient who administered pegfilgrastim on consecutive days in error. In the event of overdose, the patient should be monitored for adverse reactions [see Adverse Reactions (6.1)].

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

Carton Label One mg/0.6 mL Single-Dose Prefilled Syringe UDENYCAPRINCIPAL DISPLAY PANELCoherusBioSciences6 mg/0.6 mLNDC 70114-101-01 UDENYCA(R) pegfilgrastim-cbqvInjectionRx Only6 mg in 0.6 mL Single-Dose PrefilledSyringeFor Subcutaneous UseSterile Solution No PreservativePegylated RecombinantMethionyl Human GranulocyteColony-Stimulating Factor (PEG-r-metHuG-CSF) derivedfrom E. coli One mg/0.6 mL single-dosePrefilled Syringe. image of carton label principal panel.

PEDIATRIC USE SECTION.

8.5 Geriatric Use. Of the 932 patients with cancer who received pegfilgrastim in clinical studies, 139 (15%) were age 65 and over, and 18 (2%) were age 75 and over. No overall differences in safety or effectiveness were observed between patients age 65 and older and younger patients.

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. Carcinogenesis, Mutagenesis, Impairment of FertilityNo carcinogenicity or mutagenesis studies have been performed with pegfilgrastim products.Pegfilgrastim did not affect reproductive performance or fertility in male or female rats at cumulative weekly doses approximately to times higher than the recommended human dose (based on body surface area).

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following serious adverse reactions are discussed in greater detail in other sections of the labeling:Splenic Rupture [see Warnings and Precautions (5.1)] Acute Respiratory Distress Syndrome [see Warnings and Precautions (5.2)] Serious Allergic Reactions [see Warnings and Precautions (5.3)] Use in Patients with Sickle Cell Disorders [see Warnings and Precautions (5.4)] Glomerulonephritis [see Warnings and Precautions (5.5)] Leukocytosis [see Warnings and Precautions (5.6)] Thrombocytopenia [see Warnings and Precautions (5.7)] Capillary Leak Syndrome [see Warnings and Precautions (5.8)] Potential for Tumor Growth Stimulatory Effects on Malignant Cells [see Warnings and Precautions (5.9)] Myelodysplastic syndrome [see Warnings and Precautions (5.10)] Acute myeloid leukemia [see Warnings and Precautions (5.10)] Aortitis [see Warnings and Precautions (5.11)] Splenic Rupture [see Warnings and Precautions (5.1)] Acute Respiratory Distress Syndrome [see Warnings and Precautions (5.2)] Serious Allergic Reactions [see Warnings and Precautions (5.3)] Use in Patients with Sickle Cell Disorders [see Warnings and Precautions (5.4)] Glomerulonephritis [see Warnings and Precautions (5.5)] Leukocytosis [see Warnings and Precautions (5.6)] Thrombocytopenia [see Warnings and Precautions (5.7)] Capillary Leak Syndrome [see Warnings and Precautions (5.8)] Potential for Tumor Growth Stimulatory Effects on Malignant Cells [see Warnings and Precautions (5.9)] Myelodysplastic syndrome [see Warnings and Precautions (5.10)] Acute myeloid leukemia [see Warnings and Precautions (5.10)] Aortitis [see Warnings and Precautions (5.11)] Most common adverse reactions (>= 5% difference in incidence compared to placebo) are bone pain and pain in extremity. (6.1)To report SUSPECTED ADVERSE REACTIONS, contact Coherus BioSciences at 1-800-4UDENYCA (1-800-483-3692) or FDA at 1-800-FDA-1088 (1-800-332-1088) or www.fda.gov/medwatch. 6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.Pegfilgrastim clinical trials safety data are based upon 932 patients receiving pegfilgrastim in seven randomized clinical trials. The population was 21 to 88 years of age and 92% female. The ethnicity was 75% Caucasian, 18% Hispanic, 5% Black, and 1% Asian. Patients with breast (n 823), lung and thoracic tumors (n 53) and lymphoma (n 56) received pegfilgrastim after nonmyeloablative cytotoxic chemotherapy. Most patients received single 100 mcg/kg (n 259) or single mg (n 546) dose per chemotherapy cycle over cycles.The following adverse reaction data in Table are from randomized, double-blind, placebo-controlled study in patients with metastatic or non-metastatic breast cancer receiving docetaxel 100 mg/m2 every 21 days (Study 3). total of 928 patients were randomized to receive either mg pegfilgrastim (n 467) or placebo (n 461). The patients were 21 to 88 years of age and 99% female. The ethnicity was 66% Caucasian, 31% Hispanic, 2% Black, and <1% Asian, Native American or other.The most common adverse reactions occurring in >= 5% of patients and with between-group difference of >= 5% higher in the pegfilgrastim arm in placebo controlled clinical trials are bone pain and pain in extremity.Table 2. Adverse Reactions with >= 5% Higher Incidence in pegfilgrastim Patients Compared to Placebo in Study 3Body System Adverse ReactionPlacebo(N 461)pegfilgrastim mg SC on Day 2(N 467)Musculoskeletal and connective tissue disordersBone pain26%31%Pain in extremity4%9%LeukocytosisIn clinical studies, leukocytosis (WBC counts 100 109/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 potential for immunogenicity. The detection of antibody formation is highly 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 assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the studies described below with the incidence of antibodies in other studies or to other pegfilgrastim products may be misleading.Binding antibodies to pegfilgrastim were detected using BIAcore assay. The approximate limit of detection for this assay is 500 ng/mL. Pre-existing binding antibodies were detected in approximately 6% (51/849) of patients with metastatic breast cancer. Four of 521 pegfilgrastim-treated subjects who were negative at baseline developed binding antibodies to pegfilgrastim following treatment. None of these patients had evidence of neutralizing antibodies detected using cell-based bioassay.. 6.3 Postmarketing Experience. The following adverse reactions have been identified during post approval use of pegfilgrastim products. Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish 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)] Thrombocytopenia [see Warnings and Precautions (5.7)] Capillary leak syndrome [see Warnings and Precautions (5.8)] Injection site reactionsSweets syndrome (acute febrile neutrophilic dermatosis), cutaneous vasculitisMyelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in patients with breast and lung cancer receiving chemotherapy and/or radiotherapy [see Warnings and Precautions (5.10)] Aortitis [see Warnings and Precautions (5.11)] Alveolar hemorrhage. 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)] Thrombocytopenia [see Warnings and Precautions (5.7)] Capillary leak syndrome [see Warnings and Precautions (5.8)] Injection site reactions. Sweets syndrome (acute febrile neutrophilic dermatosis), cutaneous vasculitis. Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in patients with breast and lung cancer receiving chemotherapy and/or radiotherapy [see Warnings and Precautions (5.10)] Aortitis [see Warnings and Precautions (5.11)] Alveolar hemorrhage.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Pegfilgrastim products are colony-stimulating factors that act on hematopoietic cells by binding to specific cell surface receptors, thereby stimulating proliferation, differentiation, commitment, and end cell functional activation.. 12.2 Pharmacodynamics. Animal data and clinical data in humans suggest correlation between pegfilgrastim products exposure and the duration of severe neutropenia as predictor of efficacy. Selection of the dosing regimen of UDENYCA is based on reducing the duration of severe neutropenia.. 12.3 Pharmacokinetics. 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 factor. Patients with higher body weights experienced higher systemic exposure to pegfilgrastim after receiving dose normalized for body weight. large variability in the pharmacokinetics of pegfilgrastim was observed. The half-life of pegfilgrastim ranged from 15 to 80 hours after subcutaneous injection.Specific PopulationsNo 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 ImpairmentIn 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 Cancer Receiving Myelosuppressive ChemotherapyThe pharmacokinetics and safety of pegfilgrastim were studied in 37 pediatric patients with sarcoma in Study [see Clinical Studies 14.1]. The mean (+- standard deviation [SD]) systemic exposure (AUC0-inf) of pegfilgrastim after subcutaneous administration at 100 mcg/kg was 47.9 (+- 22.5) mcg.hr/mL in the youngest age group (0 to years, = 11), 22.0 (+- 13.1) mcg.hr/mL in the to 11 years age group (n 10), and 29.3 (+- 23.2) mcg.hr/mL in the 12 to 21 years age group (n 13). The terminal elimination half-lives of the corresponding age groups were 30.1 (+- 38.2) hours, 20.2 (+- 11.3) hours, and 21.2 (+- 16.0) hours, respectively.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. Patients with Cancer Receiving Myelosuppressive ChemotherapyPegfilgrastim was evaluated in three randomized, double-blind, controlled studies. Studies and were active-controlled studies that employed doxorubicin 60 mg/m2 and docetaxel 75 mg/m2 administered every 21 days for up to cycles for the treatment of metastatic breast cancer. Study investigated the utility of fixed dose of pegfilgrastim. Study employed weight-adjusted dose. In the absence of growth factor support, similar chemotherapy regimens have been reported to result in 100% incidence of severe neutropenia (ANC 0.5 109/L) with mean duration of to days and 30% to 40% incidence of febrile neutropenia. Based on the correlation between the duration of severe neutropenia and the incidence of febrile neutropenia found in studies with filgrastim, duration of severe neutropenia was chosen as the primary endpoint in both studies, and the efficacy of pegfilgrastim was demonstrated by establishing comparability to filgrastim-treated patients in the mean days of severe neutropenia.In Study 1, 157 patients were randomized to receive single subcutaneous injection of pegfilgrastim (6 mg) on day of each chemotherapy cycle or daily subcutaneous filgrastim (5 mcg/kg/day) beginning on day of each chemotherapy cycle. In Study 2, 310 patients were randomized to receive single subcutaneous injection of pegfilgrastim (100 mcg/kg) on day or daily subcutaneous filgrastim (5 mcg/kg/day) beginning on day of each chemotherapy cycle.Both studies met the major efficacy outcome measure of demonstrating that the mean days of severe neutropenia ofpegfilgrastim-treated patients did not exceed that of filgrastim-treated patients by more than day in cycle of chemotherapy. The mean days of cycle severe neutropenia in Study were 1.8 days in the pegfilgrastim arm compared to 1.6 days in the filgrastim arm [difference in means 0.2 (95% CI -0.2, 0.6)] and in Study were 1.7 days in the pegfilgrastim arm compared to 1.6 days in the filgrastim arm [difference in means 0.1 (95% CI -0.2, 0.4)].A secondary endpoint in both studies was days of severe neutropenia in cycles through with results similar to those for cycle 1.Study was randomized, double-blind, placebo-controlled study that employed docetaxel 100 mg/m2 administered every 21 days for up to cycles for the treatment of metastatic or non-metastatic breast cancer. In this study, 928 patients were randomized to receive single subcutaneous injection of pegfilgrastim (6 mg) or placebo on day of each chemotherapy cycle. Study met the major trial outcome measure of demonstrating that the incidence of febrile neutropenia (defined as temperature >= 38.2C and ANC <= 0.5 x109/L) was lower for pegfilgrastim-treated patients as compared to placebo-treated patients (1% versus 17%, respectively, < 0.001). The incidence of hospitalizations (1% versus 14%) and IV anti-infective use (2% versus 10%) for the treatment of febrile neutropenia was also lower in the pegfilgrastim-treated patients compared to the placebo-treated patients.Study was multicenter, randomized, open-label study to evaluate the efficacy, safety, and pharmacokinetics [see Clinical Pharmacology (12.3)] of pegfilgrastim in pediatric and young adult patients with sarcoma. Patients with sarcoma receiving chemotherapy age to 21 years were eligible. Patients were randomized to receive subcutaneous pegfilgrastim as single dose of 100 mcg/kg (n= 37) or subcutaneous filgrastim at dose mcg/kg/day (n=6) following myelosuppressive chemotherapy. Recovery of neutrophil counts was similar in the pegfilgrastim and filgrastim groups. The most common adverse reaction reported was bone pain.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. UDENYCA is contraindicated in patients with history of serious allergic reactions to pegfilgrastim products or filgrastim products. Reactions have included anaphylaxis [see Warnings and Precautions (5.3)].. Patients with history of serious allergic reaction to human granulocyte colony-stimulating factors such as pegfilgrastim or filgrastim products. (4).

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. Animal data and clinical data in humans suggest correlation between pegfilgrastim products exposure and the duration of severe neutropenia as predictor of efficacy. Selection of the dosing regimen of UDENYCA is based on reducing the duration of severe neutropenia.

DESCRIPTION SECTION.

11 DESCRIPTION. Pegfilgrastim-cbqv is covalent conjugate of recombinant methionyl human G-CSF andmonomethoxypolyethylene glycol. Recombinant methionyl human G-CSF is water-soluble, 175 amino acid protein with molecular weight of approximately 19 kilodaltons (kDa). Recombinant methionyl human G-CSF is obtained from the bacterial fermentation of strain of coli transformed with genetically engineered plasmid containing the human G-CSF gene. During the pegfilgrastim-cbqv manufacturing process, fermentation is carried out in nutrient medium containing the antibiotic kanamycin. However, kanamycin is cleared in the manufacturing process and is not detectable in the final product. To produce pegfilgrastim-cbqv, 20 kDa monomethoxypolyethylene glycol molecule is covalently bound to the N-terminal methionyl residue of recombinant methionyl 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 subcutaneous injection. The prefilled syringe does not bear graduation marks and is designed to deliver the entire contents of the syringe (6 mg/0.6 mL).Each syringe contains mg pegfilgrastim-cbqv (based on protein weight) in sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.35 mg), polysorbate 20 (0.02 mg), sodium (0.02 mg), and sorbitol (30 mg) in Water for Injection, USP.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Patients with cancer receiving myelosuppressive chemotherapy6 mg administered subcutaneously once per chemotherapy cycle. (2.1)Do not administer between 14 days before and 24 hours after administration of cytotoxic chemotherapy. (2.1)Use weight based dosing for pediatric patients weighing less than 45 kg; refer to Table 1. (2.2). mg administered subcutaneously once per chemotherapy cycle. (2.1). Do not administer between 14 days before and 24 hours after administration of cytotoxic chemotherapy. (2.1). Use weight based dosing for pediatric patients weighing less than 45 kg; refer to Table 1. (2.2). 2.1 Patients with Cancer Receiving Myelosuppressive Chemotherapy. The recommended dosage of UDENYCA is single subcutaneous injection of mg administered once per chemotherapy cycle. For dosing in pediatric patients weighing less than 45 kg, refer to Table 1. Do not administer UDENYCA between 14 days before and 24 hours after administration of cytotoxic chemotherapy.. 2.2 Administration. UDENYCA is administered subcutaneously via single-dose prefilled syringe for manual use.Prior to use, remove the carton from the refrigerator and allow the UDENYCA prefilled syringe to reach room temperature for minimum of 30 minutes. Discard any prefilled syringe left at room temperature for greater than 48 hours.Visually inspect parenteral drug products (prefilled syringe) for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer UDENYCA if discoloration or particulates are observed.The needle cap on the prefilled syringe is not made with natural rubber latex.Pediatric Patients Weighing Less than 45 kgThe UDENYCA prefilled syringe is not designed to allow for direct administration of doses less than 0.6 mL (6 mg). The syringe does not bear graduation marks which are necessary to accurately measure doses of UDENYCA less than 0.6 mL (6 mg) for direct administration to patients. Thus, the direct administration to patients requiring dosing of less than 0.6 mL (6 mg) is not recommended due to the potential for dosing errors. Refer to Table 1.Table 1. Dosing of UDENYCA for pediatric patients weighing less than 45 kgBody WeightUDENYCA DoseVolume to AdministerLess than 10 kgFor pediatric patients weighing less than 10 kg, administer 0.1 mg/kg (0.01 mL/kg) of UDENYCA See below See below 10 20 kg1.5 mg0.15 mL21 30 kg2.5 mg0.25 mL31 44 kg4 mg0.4 mL.

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. Injection: mg/0.6 mL clear, colorless, preservative-free solution in single-dose prefilled syringe for manual use only.. Injection: mg/0.6 mL in single-dose prefilled syringe formanual use only. (3).

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. UDENYCA (pegfilgrastim-cbqv) injection is clear, colorless, preservative-free solution supplied in prefilled single-dose syringe with an UltraSafe Passive(TM) Needle Guard, containing 6mg of pegfilgrastim-cbqv.The needle cap of the prefilled syringe is not made with natural rubber latex.UDENYCA is provided in dispensing pack containing one mg/0.6 mL prefilled syringe (NDC 70114-101-01).UDENYCA prefilled syringe does not bear graduation marks and is intended only to deliver the entire contents of the syringe (6 mg/0.6 mL) for direct administration. Use of the prefilled syringe is not recommended for direct administration for pediatric patients weighing less than 45 kg who require doses that are less than the full contents of the syringe.Store refrigerated between to 8C (36 to 46F) in the carton to protect from light. Do not shake. Discardsyringes stored at room temperature for more than 48 hours. Avoid freezing; if frozen, thaw in the refrigerator before administration. Discard syringe if frozen more than once.

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. UDENYCA is indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with clinically significant incidence of febrile neutropenia [see Clinical Studies (14)].Limitations of UseUDENYCA is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.. UDENYCA is leukocyte growth factor indicated to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with aclinically significant incidence of febrile neutropenia. (1) Limitations of UseUDENYCA is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use)Advise patients of the following risks and potential risks with UDENYCA [See Warnings and Precautions (5)]:Splenic rupture and splenomegalyAcute Respiratory Distress SyndromeSerious allergic reactionsSickle cell crisisGlomerulonephritisIncreased risk of Myelodysplastic Syndrome and/or Acute Myeloid Leukemia in patients with breast andlung cancer who receive pegfilgrastim in conjunction with chemotherapy and/or radiation therapyCapillary Leak SyndromeAortitisInstruct patients who self-administer UDENYCA using the single-dose prefilled syringe of the:Importance of following the Instructions for Use (see Instructions for Use).Dangers of reusing syringesImportance of following local requirements for proper disposal of used syringes.CoherusBioSciencesUDENYCA(R) (pegfilgrastim-cbqv)Manufactured by: Coherus BioSciences, Inc., Redwood City, California 94065-1442U.S. License No. 2023(C) 2021 Coherus BioSciences Inc. All rights reserved.For more information, go to www.UDENYCA.com or call 1-800-4UDENYCA (1-800-483-3692)PMD-0004, Rev. 05. Splenic rupture and splenomegaly. Acute Respiratory Distress Syndrome. Serious allergic reactions. Sickle cell crisis. Glomerulonephritis. Increased risk of Myelodysplastic Syndrome and/or Acute Myeloid Leukemia in patients with breast andlung cancer who receive pegfilgrastim in conjunction with chemotherapy and/or radiation therapy. Capillary Leak Syndrome. Aortitis. Importance of following the Instructions for Use (see Instructions for Use).. Dangers of reusing syringes. Importance of following local requirements for proper disposal of used syringes.

INSTRUCTIONS FOR USE SECTION.

Instructions for UseUDENYCA(R) (yoo-den-i-kah)(pegfilgrastim-cbqv)InjectionSingle-Dose Prefilled SyringeGuide to Parts Before UseImportant: The needle is covered by needle cap before use After UseImportantRead the Patient Information for important information you need to know aboutUDENYCA before using these Instructions for Use.Storing the UDENYCA prefilled syringeStore UDENYCA prefilled syringes in the refrigerator between 36F to 46 (2C to 8C).Keep the UDENYCA prefilled syringe in the original carton to protect from light.Do not freeze UDENYCA.If UDENYCA is accidentally frozen, allow the prefilled syringe to thaw in the refrigerator before injecting.Throw away (dispose of) any UDENYCA prefilled syringes that have been frozen more than time.Throw away (dispose of) any UDENYCA prefilled syringes that have been left out at room temperature for more than 48 hours.Keep the UDENYCA prefilled syringe out of the reach of children.Using the prefilled syringeIt is important that you do not try to give theinjection unless you or your caregiver has received training from your healthcare provider.Make sure that the name UDENYCA appears on the carton and prefilled syringe label.Check the carton and prefilled syringe label to make sure the dose strength is mg/0.6 mL.You should not inject dose of UDENYCA to children weighing less than 45 kg from UDENYCA prefilled syringe. dose less than 0.6 mL (6 mg) cannot be accurately measured using the UDENYCA prefilled syringe.Do not use prefilled syringe after theexpiration date on the label.Do not shake the prefilled syringeDo not remove the needle cap from the prefilled syringe until you are ready to inject.Do not use the prefilled syringe if the carton is open or damaged.Do not use prefilled syringe if it has been dropped on hard surface. The prefilled syringe may be broken even if you cannot see the break. Use new prefilled syringe.Do not attempt to activate the needle safety guard prior to injection Call your healthcare provider if you have anyquestions. Prepare the injection1 Remove carton from refrigerator and check expiration date1A: Remove the carton from the refrigerator and check the expiration date printed on the carton. (See Figure 3) Do not use if the expiration date has passed. 1B: Open the carton and remove the sealed syringe tray. (See Figure 4)2 Allow UDENYCA to reach room temperature and gather supplies2A: Place the sealed syringe tray on flat, clean work surface and allow it to sit at room temperature for at least 30 minutes. (See Figure 5) Do not attempt to warm up the syringe in any other way, such as microwave, hot water, or direct sunlight.2B: Gather the following supplies: (See Figure 6)Alcohol wipeCotton ball or gauze1 adhesive bandageSharps disposal container - Wash your hands and remove syringe from tray3A: Wash your hands well with soap and warm water. (See Figure 7)3B: Open the tray by peeling away the cover. Remove the prefilled syringe from the tray by grasping the middle of the syringe body and carefully pulling it out of the tray. (See Figure 8)For Safety reasons:Do not grab the plunger or the plunger head.Do not grab the needle cap. - Inspect the syringe and medicineCheck the medicine through the Inspection Window. The medicine should be clear and colorless. It is normal to see or more air bubbles in the syringe. Removal of the air is not needed. (See Figure 9) Do not use the prefilled syringe if:the medicine appears discolored or cloudy.the medicine contains lumps, flakes, or particles.it appears used or damaged.the needle cap is missing or not securely attached.the expiration date printed on the label has passed.In all cases, use new prefilled syringe and call yourhealthcare provider.Select and clean injection site5 Select and clean the injection site5A: Select the injection site. The recommended injection sites for subcutaneous injection are the: (See Figure 10)Abdomen (except for two-inch area surrounding the navel)ThighsBack of upper arms (only if someone else is giving you the injection)Upper outer area of the buttocks (only if someone else is giving you the injection) Do not inject into moles, scars, birthmarks, or areas where the skin is tender, bruised, red, or hard.If you want to use the same injection site, make sure it is not the same spot on the injection site you used for previous injection.5B: Clean the injection site with an alcohol wipe.(See Figure 11) Do not touch this area again before injection.Inject the dose6 Remove needle capRemove the needle cap by pulling it straight off.(See Figure 12) Do not remove the needle cap from theprefilled syringe until you are ready to inject.Do not twist or bend the needle cap.Do not hold the prefilled syringe by theplunger rodDo not put the needle cap back onto thesyringe. Dispose of (throw away) the needlecap in your household trashDo not use the prefilled syringe if it hasbeen dropped with the needle cap removed. - Position fingersGrasp the body of the syringe like dart (just under the finger grips) with your thumb and index fingers. (See Figure 13) Do not touch the plunger or grasp the syringe above the finger grips. - Pinch the skin and insert the needle8A: Use your free hand to gently pinch the cleaned injection site to create firm surface. (See Figure 14)8B: Hold the pinch. Insert the needle into the skin at 45 to 90-degree angle. (See Figure 15) Do not touch the plunger head whileinserting the needle into the skin.Do not touch the cleaned area of the skin 8C: After fully inserting the needle, release thepinched skin and use your free hand to stabilize the bottom of the syringe. Then move your other hand into injection position with your thumb on the plunger head. (See Figure 16)9 Push plunger head down to deliver dose9A: Using slow and constant pressure, push the plunger head down until it reaches the bottom. This will help to ensure that you receive the full dose. (See Figure 17)9B: While the needle is still inserted, slowly move your thumb back, allowing the plunger to rise. This will release the needle safety guard to safely cover the needle. Then remove the syringe from the injection site. (See Figure 18) Important: When you remove the syringe, if it looks like the medicine is still in the syringe, this means you have not received full dose. Call your healthcare provider right away. If you see drops of blood at the injection site,treat by pressing cotton ball or gauze tothe site as needed. Dispose10 Dispose of used prefilled syringesPut the used prefilled syringe into an FDA-cleared sharps disposal container right away after use. Do not throw away the syringe in the household trash. (See Figure 19)If you do not have FDA-cleared sharps disposal container, you may use householdcontainer that is:made of heavy-duty plasticcan be closed with tight-fitting, puncture-resistant lid, without sharps being able to come outupright and stable during useleak-resistantproperly labeled to warn of hazardous waste inside the container When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDAs website at: http://www.fda.gov/safesharpsdisposal.Do not reuse the prefilled syringe.Do not recycle prefilled syringes or sharps disposal container or throw them into household trash.This Instructions for Use has been approved by the U.S. Food and Drug Administration.Issued: 09/2019CoherusBioSciencesUDENYCA(R) (pegfilgrastim-cbqv) Manufactured by: Coherus BioSciences, Inc., Redwood City, California 94065-1442U.S. License No. 2023(C) 2019 Coherus BioSciences Inc. All rights reserved.For more Information go to www.UDENYCA.com or call 1-800-4UDENYCA (1-800-483-3692)PMD-0005, Rev. 02 Store UDENYCA prefilled syringes in the refrigerator between 36F to 46 (2C to 8C).. Keep the UDENYCA prefilled syringe in the original carton to protect from light.. Do not freeze UDENYCA.If UDENYCA is accidentally frozen, allow the prefilled syringe to thaw in the refrigerator before injecting.Throw away (dispose of) any UDENYCA prefilled syringes that have been frozen more than time.. If UDENYCA is accidentally frozen, allow the prefilled syringe to thaw in the refrigerator before injecting.. Throw away (dispose of) any UDENYCA prefilled syringes that have been frozen more than time.. Throw away (dispose of) any UDENYCA prefilled syringes that have been left out at room temperature for more than 48 hours.. Keep the UDENYCA prefilled syringe out of the reach of children.. It is important that you do not try to give theinjection unless you or your caregiver has received training from your healthcare provider.. Make sure that the name UDENYCA appears on the carton and prefilled syringe label.. Check the carton and prefilled syringe label to make sure the dose strength is mg/0.6 mL.. You should not inject dose of UDENYCA to children weighing less than 45 kg from UDENYCA prefilled syringe. dose less than 0.6 mL (6 mg) cannot be accurately measured using the UDENYCA prefilled syringe.. Do not use prefilled syringe after theexpiration date on the label.. Do not shake the prefilled syringe. Do not remove the needle cap from the prefilled syringe until you are ready to inject.. Do not use the prefilled syringe if the carton is open or damaged.. Do not use prefilled syringe if it has been dropped on hard surface. The prefilled syringe may be broken even if you cannot see the break. Use new prefilled syringe.. Do not attempt to activate the needle safety guard prior to injection. Alcohol wipe. Cotton ball or gauze. adhesive bandage. Sharps disposal container. Do not grab the plunger or the plunger head.. Do not grab the needle cap.. the medicine appears discolored or cloudy.. the medicine contains lumps, flakes, or particles.. it appears used or damaged.. the needle cap is missing or not securely attached.. the expiration date printed on the label has passed.. Abdomen (except for two-inch area surrounding the navel). Thighs. Back of upper arms (only if someone else is giving you the injection). Upper outer area of the buttocks (only if someone else is giving you the injection). Do not remove the needle cap from theprefilled syringe until you are ready to inject.. Do not twist or bend the needle cap.. Do not hold the prefilled syringe by theplunger rod. Do not put the needle cap back onto thesyringe. Dispose of (throw away) the needlecap in your household trash. Do not use the prefilled syringe if it hasbeen dropped with the needle cap removed.. Do not touch the plunger or grasp the syringe above the finger grips.. Do not touch the plunger head whileinserting the needle into the skin.. Do not touch the cleaned area of the skin. If you see drops of blood at the injection site,treat by pressing cotton ball or gauze tothe site as needed.. If you do not have FDA-cleared sharps disposal container, you may use householdcontainer that is:made of heavy-duty plasticcan be closed with tight-fitting, puncture-resistant lid, without sharps being able to come outupright and stable during useleak-resistantproperly labeled to warn of hazardous waste inside the container made of heavy-duty plastic. can be closed with tight-fitting, puncture-resistant lid, without sharps being able to come out. upright and stable during use. leak-resistant. properly labeled to warn of hazardous waste inside the container. When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDAs website at: http://www.fda.gov/safesharpsdisposal.. Do not reuse the prefilled syringe.. Do not recycle prefilled syringes or sharps disposal container or throw them into household trash.. image of UDENYCA before use. image of UDENYCA after use. image of storage instructions for use. image of removal from storage instructions for use. image of opening UDENYCA instructions for use. image of time to reach room temp instructions for use. image of gathering supplies instructions for use. image of proper hand washing instructions for use. image of removal of UDENYCA from tray instructions of use. image of visual inspection instructions for use. image of injection site selection instructions for use. image of cleaning injection site instructions for use. image of removal of needle cap instructions for use. image of position of fingers instructions for use. image of pinching skin of injection site instructions for use. image of proper needle insertion instructions for use. image of injection finger positioning instructions for use. image of plunger push instructions for use. image of needle retraction instructions for use. image of disposal instructions for use.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. Pegfilgrastim products are colony-stimulating factors that act on hematopoietic cells by binding to specific cell surface receptors, thereby stimulating proliferation, differentiation, commitment, and end cell functional activation.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. 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 factor. Patients with higher body weights experienced higher systemic exposure to pegfilgrastim after receiving dose normalized for body weight. large variability in the pharmacokinetics of pegfilgrastim was observed. The half-life of pegfilgrastim ranged from 15 to 80 hours after subcutaneous injection.Specific PopulationsNo 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 ImpairmentIn 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 Cancer Receiving Myelosuppressive ChemotherapyThe pharmacokinetics and safety of pegfilgrastim were studied in 37 pediatric patients with sarcoma in Study [see Clinical Studies 14.1]. The mean (+- standard deviation [SD]) systemic exposure (AUC0-inf) of pegfilgrastim after subcutaneous administration at 100 mcg/kg was 47.9 (+- 22.5) mcg.hr/mL in the youngest age group (0 to years, = 11), 22.0 (+- 13.1) mcg.hr/mL in the to 11 years age group (n 10), and 29.3 (+- 23.2) mcg.hr/mL in the 12 to 21 years age group (n 13). The terminal elimination half-lives of the corresponding age groups were 30.1 (+- 38.2) hours, 20.2 (+- 11.3) hours, and 21.2 (+- 16.0) hours, respectively.

PREGNANCY SECTION.

8.1 Pregnancy. Risk SummaryAlthough available data with UDENYCA or pegfilgrastim product use in pregnant women are insufficient to establish whether there is drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, 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 that received cumulative doses of pegfilgrastim approximately 10 times the recommended human dose (based on body surface area). In pregnant rabbits, increased embryolethality and spontaneous abortions occurred at times the maximum recommended human dose simultaneously with signs of maternal toxicity (see Data ).The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.DataAnimal DataPregnant rabbits were dosed with pegfilgrastim subcutaneously every other day during the period of organogenesis. At cumulative doses ranging from the approximate human dose to approximately times the recommended human dose (based on body surface area), treated rabbits exhibited decreased maternal food consumption, maternal weight loss, as well as reduced fetal body weights and delayed ossification of the fetal skull; however, no structural anomalies were observed in the offspring from either study. Increased incidences of post-implantation losses and spontaneous abortions (more than half the pregnancies) were observed at cumulative doses approximately times the recommended human dose, which were not seen when pregnant rabbits were exposed to the recommended human dose.Three studies were conducted in pregnant rats dosed with pegfilgrastim at cumulative doses up to approximately 10 times the recommended human dose at the following stages of gestation: during the period of organogenesis, from mating through the first half of pregnancy, and from the first trimester through delivery and lactation. No evidence of fetal loss or structural malformations was observed in any study. Cumulative doses equivalent to approximately and 10 times the recommended human dose resulted in transient evidence of wavy ribs in fetuses of treated mothers (detected at the end of gestation but no longer present in pups evaluated at the end of lactation).

RECENT MAJOR CHANGES SECTION.

Warnings and Precautions, Thrombocytopenia (5.7) 06/2021Warnings and Precautions, Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) (5.10) 06/2021.

SPL PATIENT PACKAGE INSERT SECTION.

Patient InformationUDENYCA(R) (yoo-den-i-kah)(pegfilgrastim-cbqv)InjectionSingle-Dose Prefilled SyringeWhat is UDENYCAUDENYCA is man-made form of granulocyte colony-stimulating factor (G-CSF). G-CSF is substance produced by the body. It stimulates the growth of neutrophils, type of white blood cell important in the bodys fight against infection.Do not take UDENYCAif you have had serious allergic reaction to pegfilgrastim or filgrastim products.Before you receive UDENYCA, tell your healthcare provider about all of your medical conditions, including if you:have sickle cell disorder.have kidney problems.are pregnant or plan to become pregnant. It is not known if UDENYCA will harm your unborn baby.are breastfeeding or plan to breastfeed. It is not known if UDENYCA passes into your breast milk.Tell your healthcare provider about all of the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.How will receive UDENYCAUDENYCA is given as an injection under your skin (subcutaneous injection) by healthcare provider. If your healthcare provider decides that the subcutaneous injections can be given at home by you or your caregiver, follow the detailed Instructions for Use that comes with your UDENYCA for information on how to prepare and inject dose of UDENYCA.You and your caregiver will be shown how to prepare and inject UDENYCA before you use it.You should not inject dose of UDENYCA to children weighing less than 45 kg from UDENYCA prefilledsyringe. dose less than 0.6 mL (6 mg) cannot be accurately measured using the UDENYCA prefilled syringe.If you are receiving UDENYCA because you are also receiving chemotherapy, the last dose of UDENYCA should be injected at least 14 days before and 24 hours after your dose of chemotherapy.If you miss dose of UDENYCA, talk to your healthcare provider about when you should give your next dose.What are possible side effects of UDENYCAUDENYCA may cause serious side effects, including:Spleen rupture. Your spleen may become enlarged and can rupture. ruptured spleen can cause death. Call your healthcare provider right away if you have pain in the left upper stomach area or your left shoulder.A serious lung problem called Acute Respiratory Distress Syndrome (ARDS). Call your healthcare provider or get emergency care right away if you have shortness of breath with or without fever, trouble breathing, or fast rate of breathing.Serious allergic reactions. UDENYCA can cause serious allergic reactions. These reactions can cause rash over your whole body, shortness of breath, wheezing, dizziness, swelling around your mouth or eyes, fast heart rate, and sweating. If you have any of these symptoms, stop using UDENYCA and call your healthcare provider or get emergency medical help right away.Sickle cell crises. You may have serious sickle cell crisis if you have sickle cell disorder and receive UDENYCA. Serious sickle cell crises have happened in people with sickle cell disorders receiving pegfilgrastim that has sometimes led to death. Call your healthcare provider right away if you have symptoms of sickle cell crisis such as pain or difficulty breathing.Kidney injury (glomerulonephritis). UDENYCA can cause kidney injury. Call your healthcare provider right away if you develop any of the following symptoms:swelling of your face or anklesblood in your urine or dark colored urineyou urinate less than usual Increased white blood cell count (leukocytosis). Your healthcare provider will check your blood during treatment with UDENYCA.Decreased platelet count (thrombocytopenia). Your healthcare provider will check your blood during treatment with UDENYCA. Tell your healthcare provider if you have unusual bleeding or bruising during treatment with UDENYCA. This could be sign of decreased platelet counts, which may reduce the ability of your blood to clot.Capillary Leak Syndrome. UDENYCA can cause fluid to leak from blood vessels into your bodys tissues. This condition is called Capillary Leak Syndrome (CLS). CLS can quickly cause you to have symptoms that may become life-threatening. Get emergency medical help right away if you develop any of the following symptoms:swelling or puffiness and are urinating less than usualtrouble breathingswelling of your stomach-area (abdomen) and feeling of fullnessdizziness or feeling fainta general feeling of tiredness Myelodysplastic syndrome and acute myeloid leukemia. If you have breast cancer or lung cancer, when UDENYCA is used with chemotherapy and radiation therapy, or with radiation therapy alone, you may have an increased risk of developing precancerous blood condition called myelodysplastic syndrome (MDS) or blood cancer called acute myeloid leukemia (AML).Symptoms of MDS and AML may include tiredness, fever, and easy bruising or bleeding. Call your healthcare provider if you develop these symptoms during treatment with UDENYCA.Inflammation of the aorta (aortitis). Inflammation of the aorta (the large blood vessel that transports blood from the heart to the body) has been reported in patients who received pegfilgrastim. Symptoms may include fever, abdominal pain, feeling tired, and back pain. Call your healthcare provider if you experience these symptoms.The most common side effects of UDENYCA are pain in the bones, arms, and legs.These are not all the possible side effects of UDENYCA.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.How should store UDENYCAStore UDENYCA in the refrigerator between 36F to 46F (2C to 8C).Do not freeze. If UDENYCA is accidentally frozen, allow the prefilled syringe to thaw in the refrigerator before injecting.Do not use UDENYCA prefilled syringe that has been frozen more than time. Use new UDENYCA prefilled syringe.Throw away (dispose of) any UDENYCA that has been left at room temperature, 68oF to 77oF (20oC to 25oC), for more than 48 hours or frozen more than time.Keep the prefilled syringe in the original carton to protect from light.Do not shake the prefilled syringe.Take UDENYCA out of the refrigerator 30 minutes before use and allow it to reach room temperature before preparing an injection.Keep the UDENYCA prefilled syringe out of the reach of children.General information about the safe and effective use of UDENYCA.Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflet. Do not use UDENYCA for condition for which it was not prescribed. Do not give UDENYCA to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about UDENYCA that is written for health professionals.What are the ingredients in UDENYCAActive ingredient: pegfilgrastim-cbqvInactive ingredients: acetate, polysorbate 20, sodium, and sorbitol in Water for Injection. Manufactured by: Coherus BioSciences, Inc., Redwood City, California 94065-1442U.S. License No. 2023(C) 2021 Coherus BioSciences Inc. All rights reserved. For more Information go to www.UDENYCA.com or call 1-800-4UDENYCA (1-800-483-3692)PMD-0006 Rev. 03CoherusBioSciencesThis Patient Information has been approved by the U.S. Food and Drug AdministrationRevised: 05/2021. have sickle cell disorder.. have kidney problems.. are pregnant or plan to become pregnant. It is not known if UDENYCA will harm your unborn baby.. are breastfeeding or plan to breastfeed. It is not known if UDENYCA passes into your breast milk.. UDENYCA is given as an injection under your skin (subcutaneous injection) by healthcare provider. If your healthcare provider decides that the subcutaneous injections can be given at home by you or your caregiver, follow the detailed Instructions for Use that comes with your UDENYCA for information on how to prepare and inject dose of UDENYCA.. You and your caregiver will be shown how to prepare and inject UDENYCA before you use it.. You should not inject dose of UDENYCA to children weighing less than 45 kg from UDENYCA prefilledsyringe. dose less than 0.6 mL (6 mg) cannot be accurately measured using the UDENYCA prefilled syringe.. If you are receiving UDENYCA because you are also receiving chemotherapy, the last dose of UDENYCA should be injected at least 14 days before and 24 hours after your dose of chemotherapy.. If you miss dose of UDENYCA, talk to your healthcare provider about when you should give your next dose.. Spleen rupture. Your spleen may become enlarged and can rupture. ruptured spleen can cause death. Call your healthcare provider right away if you have pain in the left upper stomach area or your left shoulder.. serious lung problem called Acute Respiratory Distress Syndrome (ARDS). Call your healthcare provider or get emergency care right away if you have shortness of breath with or without fever, trouble breathing, or fast rate of breathing.. Serious allergic reactions. UDENYCA can cause serious allergic reactions. These reactions can cause rash over your whole body, shortness of breath, wheezing, dizziness, swelling around your mouth or eyes, fast heart rate, and sweating. If you have any of these symptoms, stop using UDENYCA and call your healthcare provider or get emergency medical help right away.. Sickle cell crises. You may have serious sickle cell crisis if you have sickle cell disorder and receive UDENYCA. Serious sickle cell crises have happened in people with sickle cell disorders receiving pegfilgrastim that has sometimes led to death. Call your healthcare provider right away if you have symptoms of sickle cell crisis such as pain or difficulty breathing.. Kidney injury (glomerulonephritis). UDENYCA can cause kidney injury. Call your healthcare provider right away if you develop any of the following symptoms:swelling of your face or anklesblood in your urine or dark colored urineyou urinate less than usual swelling of your face or ankles. blood in your urine or dark colored urine. you urinate less than usual. Increased white blood cell count (leukocytosis). Your healthcare provider will check your blood during treatment with UDENYCA.. Decreased platelet count (thrombocytopenia). Your healthcare provider will check your blood during treatment with UDENYCA. Tell your healthcare provider if you have unusual bleeding or bruising during treatment with UDENYCA. This could be sign of decreased platelet counts, which may reduce the ability of your blood to clot.. Capillary Leak Syndrome. UDENYCA can cause fluid to leak from blood vessels into your bodys tissues. This condition is called Capillary Leak Syndrome (CLS). CLS can quickly cause you to have symptoms that may become life-threatening. Get emergency medical help right away if you develop any of the following symptoms:swelling or puffiness and are urinating less than usualtrouble breathingswelling of your stomach-area (abdomen) and feeling of fullnessdizziness or feeling fainta general feeling of tiredness swelling or puffiness and are urinating less than usual. trouble breathing. swelling of your stomach-area (abdomen) and feeling of fullness. dizziness or feeling faint. general feeling of tiredness. Myelodysplastic syndrome and acute myeloid leukemia. If you have breast cancer or lung cancer, when UDENYCA is used with chemotherapy and radiation therapy, or with radiation therapy alone, you may have an increased risk of developing precancerous blood condition called myelodysplastic syndrome (MDS) or blood cancer called acute myeloid leukemia (AML).Symptoms of MDS and AML may include tiredness, fever, and easy bruising or bleeding. Call your healthcare provider if you develop these symptoms during treatment with UDENYCA.. Inflammation of the aorta (aortitis). Inflammation of the aorta (the large blood vessel that transports blood from the heart to the body) has been reported in patients who received pegfilgrastim. Symptoms may include fever, abdominal pain, feeling tired, and back pain. Call your healthcare provider if you experience these symptoms.. Store UDENYCA in the refrigerator between 36F to 46F (2C to 8C).. Do not freeze. If UDENYCA is accidentally frozen, allow the prefilled syringe to thaw in the refrigerator before injecting.. Do not use UDENYCA prefilled syringe that has been frozen more than time. Use new UDENYCA prefilled syringe.. Throw away (dispose of) any UDENYCA that has been left at room temperature, 68oF to 77oF (20oC to 25oC), for more than 48 hours or frozen more than time.. Keep the prefilled syringe in the original carton to protect from light.. Do not shake the prefilled syringe.. Take UDENYCA out of the refrigerator 30 minutes before use and allow it to reach room temperature before preparing an injection.

SPL UNCLASSIFIED SECTION.

2.1 Patients with Cancer Receiving Myelosuppressive Chemotherapy. The recommended dosage of UDENYCA is single subcutaneous injection of mg administered once per chemotherapy cycle. For dosing in pediatric patients weighing less than 45 kg, refer to Table 1. Do not administer UDENYCA between 14 days before and 24 hours after administration of cytotoxic chemotherapy.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Risk SummaryAlthough available data with UDENYCA or pegfilgrastim product use in pregnant women are insufficient to establish whether there is drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, 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 that received cumulative doses of pegfilgrastim approximately 10 times the recommended human dose (based on body surface area). In pregnant rabbits, increased embryolethality and spontaneous abortions occurred at times the maximum recommended human dose simultaneously with signs of maternal toxicity (see Data ).The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.DataAnimal DataPregnant rabbits were dosed with pegfilgrastim subcutaneously every other day during the period of organogenesis. At cumulative doses ranging from the approximate human dose to approximately times the recommended human dose (based on body surface area), treated rabbits exhibited decreased maternal food consumption, maternal weight loss, as well as reduced fetal body weights and delayed ossification of the fetal skull; however, no structural anomalies were observed in the offspring from either study. Increased incidences of post-implantation losses and spontaneous abortions (more than half the pregnancies) were observed at cumulative doses approximately times the recommended human dose, which were not seen when pregnant rabbits were exposed to the recommended human dose.Three studies were conducted in pregnant rats dosed with pegfilgrastim at cumulative doses up to approximately 10 times the recommended human dose at the following stages of gestation: during the period of organogenesis, from mating through the first half of pregnancy, and from the first trimester through delivery and lactation. No evidence of fetal loss or structural malformations was observed in any study. Cumulative doses equivalent to approximately and 10 times the recommended human dose resulted in transient evidence of wavy ribs in fetuses of treated mothers (detected at the end of gestation but no longer present in pups evaluated at the end of lactation).. 8.2 Lactation. Risk SummaryThere are no data on the presence of pegfilgrastim products in human milk, the effects on the breastfed child, or the effects on milk production. Other filgrastim products are secreted poorly into breast milk, and filgrastim products are not orally absorbed by neonates. The developmental and health benefits of breastfeeding should be considered along with the mothers clinical need for UDENYCA and any potential adverse effects on the breastfed child from UDENYCA or from the underlying maternal condition.. 8.4 Pediatric Use. The safety and effectiveness of pegfilgrastim have been established in pediatric patients. No overall differences in safety were identified between adult and pediatric patients with pegfilgrastim based on postmarketing surveillance and review of the scientific literature.Use of pegfilgrastim in pediatric patients for chemotherapy-induced neutropenia is based on adequate and well controlled studies in adults with additional pharmacokinetic and safety data in pediatric patients with sarcoma [see Clinical Pharmacology (12.3) and Clinical Studies (14)].. 8.5 Geriatric Use. Of the 932 patients with cancer who received pegfilgrastim in clinical studies, 139 (15%) were age 65 and over, and 18 (2%) were age 75 and over. No overall differences in safety or effectiveness were observed between patients age 65 and older and younger patients.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Fatal splenic rupture: Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture (5.1)Acute respiratory distress syndrome (ARDS): Evaluate patients who develop fever, lung infiltrates, or respiratory distress. Discontinue UDENYCA in patients with ARDS. (5.2)Serious allergic reactions, including anaphylaxis: Permanently discontinue UDENYCA in patients with serious allergic reactions. (5.3)Fatal sickle cell crises: Discontinue UDENYCA if sickle cell crisis occurs. (5.4)Glomerulonephritis: Evaluate and consider dose-reduction or interruption of UDENYCA if causality is likely. (5.5)Thrombocytopenia: Monitor platelet count (5.7)Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML): Monitor patients with breast and lung cancer using UDENYCA in conjunction with chemotherapy and/or radiotherapy for signs and symptoms of MDS/AML. (5.10). Fatal splenic rupture: Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture (5.1). Acute respiratory distress syndrome (ARDS): Evaluate patients who develop fever, lung infiltrates, or respiratory distress. Discontinue UDENYCA in patients with ARDS. (5.2). Serious allergic reactions, including anaphylaxis: Permanently discontinue UDENYCA in patients with serious allergic reactions. (5.3). Fatal sickle cell crises: Discontinue UDENYCA if sickle cell crisis occurs. (5.4). Glomerulonephritis: Evaluate and consider dose-reduction or interruption of UDENYCA if causality is likely. (5.5). Thrombocytopenia: Monitor platelet count (5.7). Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML): Monitor patients with breast and lung cancer using UDENYCA in conjunction with chemotherapy and/or radiotherapy for signs and symptoms of MDS/AML. (5.10). 5.1 Splenic Rupture. Splenic rupture, including fatal cases, can occur following the administration of pegfilgrastim products. Evaluate for an enlarged spleen or splenic rupture in patients who report left upper abdominal or shoulder pain after receiving UDENYCA.. 5.2 Acute Respiratory Distress Syndrome. Acute respiratory distress syndrome (ARDS) can occur in patients receiving pegfilgrastim products. Evaluate patients who develop fever and lung infiltrates or respiratory distress after receiving UDENYCA for ARDS. Discontinue UDENYCA in patients with ARDS.. 5.3 Serious Allergic Reactions. Serious allergic reactions, including anaphylaxis, can occur in patients receiving pegfilgrastim products. The majority of reported events occurred upon initial exposure. Allergic reactions, including anaphylaxis, can recur within days after the discontinuation of initial anti-allergic treatment. Permanently discontinue UDENYCA in patients with serious allergic reactions. Do not administer UDENYCA to patients with history of serious allergic reactions to pegfilgrastim products or filgrastim products.. 5.4 Use in Patients with Sickle Cell Disorders. Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving pegfilgrastim products. Discontinue UDENYCA if sickle cell crisis occurs.. 5.5 Glomerulonephritis. Glomerulonephritis has occurred in patients receiving pegfilgrastim products. The diagnoses were based upon azotemia, hematuria (microscopic and macroscopic), proteinuria, and renal biopsy. Generally, events of glomerulonephritis resolved after dose reduction or discontinuation of pegfilgrastim products. If glomerulonephritis is suspected, evaluate for cause. If causality is likely, consider dose-reduction or interruption of UDENYCA.. 5.6 Leukocytosis. White blood cell (WBC) counts of 100 109/L or greater have been observed in patients receiving pegfilgrastim products. Monitoring of complete blood count (CBC) during UDENYCA therapy is recommended.. 5.7 Thrombocytopenia. Thrombocytopenia has been reported in patients receiving pegfilgrastim products. Monitor platelet counts.. 5.8 Capillary Leak Syndrome. Capillary leak syndrome has been reported after G-CSF administration, including pegfilgrastim products, and is characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration. Episodes vary in frequency, severity and may be life-threatening if treatment is delayed. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include need for intensive care.. 5.9 Potential for Tumor Growth Stimulatory Effects on Malignant Cells. The granulocyte colony-stimulating factor (G-CSF) receptor through which pegfilgrastim products and filgrastim products act has been found on tumor cell lines. The possibility that pegfilgrastim products act as growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which pegfilgrastim products are not approved, cannot be excluded.. 5.10 Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) in Patients with Breast and Lung Cancer. MDS and AML have been associated with the use of pegfilgrastim products in conjunction with chemotherapy and/or radiotherapy in patients with breast and lung cancer. Monitor patients for signs and symptoms of MDS/AML in these settings.. 5.11 Aortitis. Aortitis has been reported in patients receiving pegfilgrastim products. It may occur as early as the first week after start of therapy. Manifestations may include generalized signs and symptoms such as fever, abdominal pain, malaise, back pain, and increased inflammatory markers (e.g., c-reactive protein and white blood cell count). Consider aortitis in patients who develop these signs and symptoms without known etiology. Discontinue UDENYCA if aortitis is suspected.. 5.12 Nuclear Imaging. Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. This should be considered when interpreting bone imaging results.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. No carcinogenicity or mutagenesis studies have been performed with pegfilgrastim products.Pegfilgrastim did not affect reproductive performance or fertility in male or female rats at cumulative weekly doses approximately to times higher than the recommended human dose (based on body surface area).