NDC 67457-833 Fulphila

Pegfilgrastim

NDC Product Code 67457-833

NDC CODE: 67457-833

Proprietary Name: Fulphila What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Pegfilgrastim What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • Pegfilgrastim is a man-made version of a certain natural substance made in your body. It is used to help your body make more white blood cells. White blood cells are important to help you fight off infections. Pegfilgrastim is given to people whose ability to make white blood cells is reduced due to chemotherapy. Some brands may also be used to increase white blood cells after exposure to large amounts of radiation. This monograph is about the following pegfilgrastim products: pegfilgrastim, pegfilgrastim-cbqv, pegfilgrastim-jmdb, and pegfilgrastim-bmez.

NDC Code Structure

  • 67457 - Mylan Institutional Llc

NDC 67457-833-06

Package Description: 1 SYRINGE in 1 CARTON > .6 mL in 1 SYRINGE

NDC Product Information

Fulphila with NDC 67457-833 is a a human prescription drug product labeled by Mylan Institutional Llc. The generic name of Fulphila is pegfilgrastim. The product's dosage form is injection and is administered via subcutaneous form. The RxNorm Crosswalk for this NDC code indicates multiple RxCUI concepts are associated to this product: 2048020 and 2048025.

Dosage Form: Injection - A sterile preparation intended for parenteral use; five distinct classes of injections exist as defined by the USP.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Fulphila Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.


Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • ACETIC ACID (UNII: Q40Q9N063P)
  • POLYSORBATE 20 (UNII: 7T1F30V5YH)
  • SODIUM HYDROXIDE (UNII: 55X04QC32I)
  • SORBITOL (UNII: 506T60A25R)
  • WATER (UNII: 059QF0KO0R)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Subcutaneous - Administration beneath the skin; hypodermic. Synonymous with the term SUBDERMAL.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Granulocyte Colony-Stimulating Factor - [CS]
  • Granulocyte-Macrophage Colony-Stimulating Factor - [CS]
  • Increased Myeloid Cell Production - [PE] (Physiologic Effect)
  • Leukocyte Growth Factor - [EPC] (Established Pharmacologic Class)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Mylan Institutional Llc
Labeler Code: 67457
FDA Application Number: BLA761075 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: BLA - A product marketed under an approved Biologic License Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 07-09-2018 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2022 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

* Please review the disclaimer below.

Fulphila Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1.1 Patients With Cancer Receiving Myelosuppressive Chemotherapy

Fulphila 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 a clinically significant incidence of febrile neutropenia [see Clinical Studies (14.1)].

Limitations Of Use

Fulphila is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

2.1 Patients With Cancer Receiving Myelosuppressive Chemotherapy

The recommended dosage of Fulphila is a single subcutaneous injection of 6 mg administered once per chemotherapy cycle. For dosing in pediatric patients weighing less than 45 kg, refer to Table 1. Do not administer Fulphila between 14 days before and 24 hours after administration of cytotoxic chemotherapy.

2.2 Administration

Fulphila is administered subcutaneously via a single-dose prefilled syringe for manual use. Prior to use‚ remove the carton from the refrigerator and allow the Fulphila prefilled syringe to reach room temperature for a minimum of 30 minutes. Discard any prefilled syringe left at room temperature for greater than 72 hours. Visually inspect parenteral drug products (prefilled syringe) for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not administer Fulphila if discoloration or particulates are observed.

Pediatric Patients Weighing Less Than 45 Kg

The Fulphila 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 Fulphila 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 Fulphila for pediatric patients weighing less than 45 kg Body WeightFulphila DoseVolume to AdministerLess than 10 kgFor pediatric patients weighing less than 10 kg, administer 0.1 mg/kg (0.01 mL/kg) of Fulphila. See belowSee below10 to 20 kg1.5 mg0.15 mL21 to 30 kg2.5 mg0.25 mL31 to 44 kg4 mg0.4 mL

3 Dosage Forms And Strengths

  • •Injection: 6 mg/0.6 mL clear, colorless solution of Fulphila in a single-dose prefilled syringe for manual use only.

4 Contraindications

Fulphila is contraindicated in patients with a history of serious allergic reactions to pegfilgrastim products or filgrastim products [see Warnings and Precautions (5.3)]. Reactions have included anaphylaxis [see Warnings and Precautions (5.3)].

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 Fulphila.

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 Fulphila, for ARDS. Discontinue Fulphila 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 Fulphila in patients with serious allergic reactions. Do not administer Fulphila to patients with a 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.

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 Fulphila.

5.6 Leukocytosis

White blood cell (WBC) counts of 100 x 109/L or greater have been observed in patients receiving pegfilgrastim products. Monitoring of complete blood count (CBC) during therapy with Fulphila is recommended.

5.7 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 a need for intensive care.

5.8 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 a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which pegfilgrastim products are not approved, cannot be excluded.

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)] •Capillary Leak Syndrome [See Warnings and Precautions (5.7)] •Potential for Tumor Growth Stimulatory Effects on Malignant Cells [See Warnings and Precautions (5.8)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a 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 a single 100 mcg/kg (n = 259) or a single 6 mg (n = 546) dose per chemotherapy cycle over 4 cycles.The following adverse reaction data in Table 2 are from a 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). A total of 928 patients were randomized to receive either 6 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 a 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 6 mg SC on Day 2(N = 467)Musculoskeletal and connective tissue disorders     Bone pain26%31%     Pain in extremity4%9%

Leukocytosis

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 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 to pegfilgrastim in the studies described below with the incidence of antibodies in other studies or to other products may be misleading. Binding antibodies to pegfilgrastim were detected using a 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 4 patients had evidence of neutralizing antibodies detected using a 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 a population of uncertain size, it is not always possible to reliably estimate 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, and 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

7 Drug Interactions

No formal drug interaction studies between pegfilgrastim products and other drugs have been performed. Increased hematopoietic activity of the bone marrow in response to growth factor therapy may result in transiently positive bone-imaging changes. Consider these findings when interpreting bone-imaging results.

Risk Summary

Although available data with Fulphila or pegfilgrastim product use in pregnant women are insufficient to establish whether there is a 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 4 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 a 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.

There are no data on the presence of pegfilgrastim 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 absorbed orally by neonates. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Fulphila and any potential adverse effects on the breastfed child from Fulphila or from the underlying maternal condition.

Human Data

Retrospective studies indicate that exposure to pegfilgrastim is without significant adverse effect on fetal outcomes and neutropenia. Preterm deliveries have been reported in some patients.

Animal Data

Pregnant 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 4 times the recommended human dose (based on body surface area), the 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 4 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 3 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).

8.4 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 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 (14.1)].

8.5 Geriatric Use

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

10 Overdosage

Overdosage of pegfilgrastim products may result in leukocytosis and bone pain. Events of edema, dyspnea, and pleural effusion have been reported in a single patient who administered pegfilgrastim on 8 consecutive days in error. In the event of overdose, the patient should be monitored for adverse reactions [see Adverse Reactions (6)].

11 Description

Pegfilgrastim-jmdb is a covalent conjugate of recombinant methionyl human G-CSF and monomethoxypolyethylene glycol. Recombinant methionyl human G-CSF is a water-soluble 175 amino acid protein with a molecular weight of approximately 19 kilodaltons (kD). Recombinant methionyl human G-CSF is obtained from the bacterial fermentation of a strain of E coli transformed with a genetically engineered plasmid containing the human G-CSF gene. To produce pegfilgrastim-jmdb a 20 kD monomethoxypolyethylene glycol molecule is covalently bound to the N-terminal methionyl residue of recombinant methionyl human G-CSF. The average molecular weight of pegfilgrastim-jmdb is approximately 39 kD. Fulphila (pegfilgrastim-jmdb) injection is intended for subcutaneous use only and is supplied in a single-dose prefilled syringe with a 29 gauge needle, with UltraSafe Passive Plus™ Needle Guard. The prefilled syringe does not bear graduation marks and is designed to deliver the entire contents of the syringe (6 mg/0.6 mL). The delivered 0.6 mL dose from the prefilled syringe contains 6 mg pegfilgrastim-jmdb (based on protein mass only) in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.7 mg), D-sorbitol (30 mg), polysorbate 20 (0.024 mg) and sodium (0.01 mg) in Water for Injection, USP.

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 a correlation between pegfilgrastim products exposure and the duration of severe neutropenia as a predictor of efficacy. Selection of the dosing regimen of Fulphila is based on reducing the duration of severe neutropenia.

12.3 Pharmacokinetics

The pharmacokinetics of pegfilgrastim was studied in 379 patients with cancer. The pharmacokinetics of pegfilgrastim was 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 [see Use in Specific Populations (8.6)].

Pediatric Patients With Cancer Receiving Myelosuppressive Chemotherapy

The pharmacokinetics and safety of pegfilgrastim were studied in 37 pediatric patients with sarcoma in Study 4 [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 5 years, n = 11), 22.0 (± 13.1) mcg·hr/mL in the (6 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.

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 6 to 9 times higher than the recommended human dose (based on body surface area).

14.1 Patients With Cancer Receiving Myelosuppressive Chemotherapy

Pegfilgrastim was evaluated in three randomized, double-blind, controlled studies. Studies 1 and 2 were active-controlled studies that employed doxorubicin 60 mg/m2 and docetaxel 75 mg/m2 administered every 21 days for up to 4 cycles for the treatment of metastatic breast cancer. Study 1 investigated the utility of a fixed dose of pegfilgrastim. Study 2 employed a weight-adjusted dose. In the absence of growth factor support, similar chemotherapy regimens have been reported to result in a 100% incidence of severe neutropenia (ANC < 0.5 x 109/L) with a mean duration of 5 to 7 days and a 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 a single subcutaneous injection of pegfilgrastim (6 mg) on day 2 of each chemotherapy cycle or daily subcutaneous filgrastim (5 mcg/kg/day) beginning on day 2 of each chemotherapy cycle. In Study 2, 310 patients were randomized to receive a single subcutaneous injection of pegfilgrastim (100 mcg/kg) on day 2 or daily subcutaneous filgrastim (5 mcg/kg/day) beginning on day 2 of each chemotherapy cycle. Both studies met the major efficacy outcome measure of demonstrating that the mean days of severe neutropenia of pegfilgrastim-treated patients did not exceed that of filgrastim-treated patients by more than 1 day in cycle 1 of chemotherapy. The mean days of cycle 1 severe neutropenia in Study 1 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 2 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 2 through 4 with results similar to those for cycle 1. Study 3 was a randomized, double-blind, placebo-controlled study that employed docetaxel 100 mg/m2 administered every 21 days for up to 4 cycles for the treatment of metastatic or non-metastatic breast cancer. In this study, 928 patients were randomized to receive a single subcutaneous injection of pegfilgrastim (6 mg) or placebo on day 2 of each chemotherapy cycle. Study 3 met the major trial outcome measure of demonstrating that the incidence of febrile neutropenia (defined as temperature ≥ 38.2°C and ANC ≤ 0.5 x109/L) was lower for pegfilgrastim-treated patients as compared to placebo-treated patients (1% versus 17%, respectively, p < 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 4 was a 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 0 to 21 years were eligible. Patients were randomized to receive subcutaneous pegfilgrastim as a single-dose of 100 mcg/kg (n = 37) or subcutaneous filgrastim at a dose 5 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.

16 How Supplied/Storage And Handling

Fulphila single-dose prefilled syringe for manual use Fulphila (pegfilgrastim-jmdb) Injection is a clear, colorless solution supplied in a prefilled single-dose syringe for manual use containing 6 mg pegfilgrastim-jmdb, supplied with a 29 gauge, 1/2-inch needle with an UltraSafe Passive Plus™ Needle Guard. Fulphila is provided in a dispensing pack containing one sterile 6 mg/0.6 mL prefilled syringe.NDC 67457-833-06Fulphila 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 2° to 8°C (36° to 46°F) in the carton to protect from light. Do not shake. Discard syringes stored at room temperature for more than 72 hours. Avoid freezing; if frozen, thaw in the refrigerator before administration. Discard syringe if frozen more than once.

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 Fulphila: •Splenic rupture and splenomegaly •Acute Respiratory Distress Syndrome •Serious allergic reactions •Sickle cell crisis •Glomerulonephritis •Capillary Leak Syndrome Instruct patients who self-administer Fulphila using the single-dose prefilled syringe of the: •Importance of following the Instructions for Use. •Dangers of reusing syringes. •Importance of following local requirements for proper disposal of used syringes.Manufactured by: Mylan GmbHZurich, Switzerland, CH-8050U.S. License No. 2062

Patient Information

  • Fulphila™ (FULL-fil-ah)(pegfilgrastim-jmdb) InjectionSingle-Dose Prefilled SyringeWhat is Fulphila?Fulphila is a man-made form of granulocyte colony-stimulating factor (G-CSF). G-CSF is a substance produced by the body. It stimulates the growth of neutrophils, a type of white blood cell important in the body’s fight against infection.Do not take Fulphila if you have had a serious allergic reaction to pegfilgrastim or filgrastim products. Before you receive Fulphila, tell your healthcare provider about all of your medical conditions, including if you: •have a sickle cell disorder. •have kidney problems. •are pregnant or plan to become pregnant. It is not known if Fulphila will harm your unborn baby. •are breastfeeding or plan to breastfeed. It is not known if pegfilgrastim 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 I receive Fulphila? •Fulphila is given as an injection under your skin (subcutaneous injection) by a 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 Fulphila for information on how to prepare and inject a dose of Fulphila. •You and your caregiver will be shown how to prepare and inject Fulphila before you use it. •You should not inject a dose of Fulphila to children weighing less than 45 kg from a Fulphila prefilled syringe. A dose less than 0.6 mL (6 mg) cannot be accurately measured using the Fulphila prefilled syringe. •If you are receiving Fulphila because you are also receiving chemotherapy, the last dose of Fulphila should be injected at least 14 days before and 24 hours after your dose of chemotherapy. •If you miss a dose of Fulphila, talk to your healthcare provider about when you should give your next dose.What are possible side effects of Fulphila? Fulphila may cause serious side effects, including: •Spleen rupture. Your spleen may become enlarged and can rupture. A 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 a fever, trouble breathing, or a fast rate of breathing. •Serious allergic reactions. Fulphila can cause serious allergic reactions. These reactions can cause a 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 Fulphila and call your healthcare provider or get emergency medical help right away. •Sickle cell crises. You may have a serious sickle cell crisis if you have a sickle cell disorder and receive Fulphila. Serious sickle cell crises have happened in people with sickle cell disorders receiving Fulphila 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). Fulphila can cause kidney injury. Call your healthcare provider right away if you develop any of the following symptoms: oswelling of your face or ankles oblood in your urine or dark colored urine oyou urinate less than usual •Increased white blood cell count (leukocytosis). Your healthcare provider will check your blood during treatment with Fulphila. •Capillary Leak Syndrome. Fulphila can cause fluid to leak from blood vessels into your body’s 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: oswelling or puffiness and are urinating less than usual otrouble breathing oswelling of your stomach-area (abdomen) and feeling of fullness odizziness or feeling faint oa general feeling of tiredness The most common side effects of Fulphila are pain in the bones, arms, and legs. These are not all the possible side effects of Fulphila. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.How should I store Fulphila? •Store Fulphila in the refrigerator between 36°F to 46°F (2°C to 8°C). •Do not freeze. If Fulphila is accidently frozen, allow the prefilled syringe to thaw in the refrigerator before injecting. •Do not use a Fulphila prefilled syringe that has been frozen more than 1 time. Use a new Fulphila prefilled syringe. •Throw away (dispose of) any Fulphila that has been left at room temperature, 68°F to 77ºF (20°C to 25ºC) for more than 72 hours or frozen more than 1 time. •Keep the prefilled syringe in the original carton to protect from light. •Do not shake the prefilled syringe. •Take Fulphila out of the refrigerator 30 minutes before use and allow it to reach room temperature before preparing an injection. Keep the Fulphila prefilled syringe out of the reach of children. General information about the safe and effective use of Fulphila. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Fulphila for a condition for which it was not prescribed. Do not give Fulphila 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 Fulphila that is written for health professionals.What are the ingredients in Fulphila? Active ingredient: pegfilgrastim-jmdbInactive ingredients: acetate, D-sorbitol, polysorbate 20, and sodium in Water for Injection. Manufactured by: Mylan GmbH, Zurich, Switzerland, CH-8050 U.S. License No. 2062Product of India. Code No.: KR/DRUGS/KTK/28D/7/2006 Distributed by: Mylan Institutional LLC, Rockford, IL 61103 U.S.A. For more information, go to www.fulphila.com or call 1-833-695-2623. This Patient Information has been approved by the U.S. Food and Drug Administration.      Issued: 6/2018Manufactured by:Mylan GmbHZurich, Switzerland, CH-8050U.S. License No. 2062Product of IndiaCode No.: KR/DRUGS/KTK/28D/7/2006Distributed by: Mylan Institutional LLCRockford, IL 61103 U.S.A.Revised: 6/2018B:PEGFIL:R1  Instructions for UseFULPHILATM (FULL-fil-ah)(pegfilgrastim-jmdb)injection, for subcutaneous useSingle-Dose Prefilled SyringeGuide to PartsBefore UseAfter UseImportant: The needle is covered by the gray needle cap before use.Important InformationRead the Patient Information for important information you need to know about Fulphila before using these Instructions for Use. Storing the Fulphila prefilled syringe •Store Fulphila in the refrigerator between 36ºF to 46ºF (2ºC to 8ºC). •Do not freeze. If Fulphila is accidentally frozen, allow the prefilled syringe to thaw in the refrigerator before injecting. •Do not use a Fulphila prefilled syringe that has been frozen more than 1 time.Use a new Fulphila prefilled syringe. •Throw away (dispose of) any Fulphila that has been left at room temperature, 68ºF to 77ºF (20ºC to 25ºC) for more than 72 hours or frozen more than 1 time. See Step 4: Disposing of used prefilled syringes. •Keep the prefilled syringe in the original carton to protect from light. •For questions about storage, contact your healthcare provider or pharmacist. •Keep the Fulphila prefilled syringe out of the reach of children.Before you use a Fulphila prefilled syringe, read this important information: •It is important that you do not try to give yourself the injection unless you have received training from your healthcare provider. •The prefilled syringe has a needle safety guard that will be activated to cover the needle after the injection is given. The needle guard will help prevent needlestick injuries to anyone who handles the prefilled syringe after the injection has been given. •Make sure that the name Fulphila appears on the carton and prefilled syringe label. Fulphila is given as an injection into the tissue just under the skin (subcutaneous injection). •You should not inject a dose of Fulphila to children weighing less than 45 kg from a Fulphila prefilled syringe. A dose less than 0.6 mL (6 mg) cannot be accurately measured using the Fulphila prefilled syringe. •Do not use a prefilled syringe after the expiration date on the label. •Do not shake the prefilled syringe. •Do not use the prefilled syringe if the carton is open or damaged. •Do not remove the gray needle cap from the prefilled syringe until you are ready to inject. •Do not use the prefilled syringe if it has been dropped on a hard surface. The syringe may be broken even if you cannot see the break. Use a new prefilled syringe. •Do not attempt to activate the prefilled syringe prior to injection. •Do not attempt to remove the needle safety guard from the prefilled syringe. •Do not attempt to remove the label from the prefilled syringe barrel before injecting your dose of Fulphila.Call your healthcare provider if you have any questions.Step 1: Gather suppliesA - Find a clean, well-lit and flat work surface, such as a table. B - Take the prefilled syringe carton out of the refrigerator and place it on your clean work surface. Allow it to reach room temperature for 30 minutes before giving an injection. C - Remove the prefilled syringe tray from the carton. D - Wash your hands thoroughly with soap and water.  E - Gather the supplies for the injection: •1 alcohol wipe •1 cotton ball or gauze pad •1 adhesive bandage •an FDA-cleared sharps disposal containerStep 2: Prepare for injectionF - Open the tray by peeling away the cover. Grab theneedle safety guard to remove the prefilled syringe from the tray.  For safety reasons: •Do not grab the plunger rod. •Do not grasp the gray needle cap.G - Inspect the medicine and prefilled syringe.       Make sure the medicine in the prefilled syringe is clear and colorless. Do not use the prefilled syringe if: •The medicine is cloudy or discolored, or contains flakes or particles. •The prefilled syringe has been dropped. •Any part appears cracked or broken. •The gray needle cap is missing or not securely attached. •The expiration date printed on the label haspassed.In all cases, use a new prefilled syringe and call your healthcare provider.H - Prepare and clean the injection site.      There are 4 injection sites that you can use: •thigh •stomach area (abdomen), except for a 2-inch area right around the navel (belly button) •upper outer area of the buttocks (only if someone else is giving you the injection), and •the outer area of the upper arm (only if someone else is giving you the injection).Clean the injection site with an alcohol wipe. Let the skin dry. •Do not touch this area again before injecting. •Do not inject into areas where the skin is tender, bruised, red, or hard. Avoid injecting into areas with scars or stretch marks. •If you want to use the same injection site, make sure it is not the same spot on the injection site you used for a previous injection.I - Hold the prefilled syringe by the needle safety guard.When ready, carefully pull the gray needle cap straight off and away from the body. •Do not twist or bend the gray needle cap. •Do not hold the prefilled syringe by the plunger rod. •Do not put the gray needle cap back onto the prefilled syringe. Dispose of (throw away) the gray needle cap in your household trash.Step 3: Inject the doseJ - Pinch the cleaned injection site to create a firm surface. !Keep skin pinched while injecting.K - Hold the pinch. Insert the needle into the skin between 45 to 90 degrees. •Do not touch the cleaned area of the skinL - Using slow and constant pressure, push the plunger rod until it reaches the bottom.  !The plunger must be pushed fully in order to inject the full dose.M - Once the entire dose has been injected, the needle safety guard will be triggered. You can do either of the following: •Release the plunger until the entire needle is covered and then remove the needle from the injection site.or •Gently remove the needle from the injection site and release the plunger until the entire needle is covered by the needle safety guard.After releasing the plunger, the needle safety guard will safely cover the injection needle. •Once the needle has been removed from the injection site, dispose of the syringe and needle in your sharps disposal container right away. See “Step 4: Disposing of used prefilled syringes”.oIf the needle safety guard is not activated or only partially activated, discard the product (without replacing the needle cap). See “Step 4: Disposing of used prefilled syringes”.oIf your injection is given by another person, they should also be careful when removing the needle from your skin in order to prevent accidental needlestick injury and possible infections.oWhen you remove the syringe, if it looks like the medicine is still in the syringe barrel, this means you have not received the full dose. Call your healthcare provider right away.N - Examine the injection site. If there is blood, press a cotton ball or gauze pad on the injection site. Do not rub the injection site. Apply an adhesive bandage if needed.Step 4: Disposing of used prefilled syringes •Put the used prefilled syringe in an FDA-cleared sharps disposal container right away after use. Do not throw away the syringe in the household trash. •If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:omade of heavy-duty plasticocan be closed with a tight-fitting, puncture-resistant lid without sharps being able to come outoupright and stable during useoleak-resistantoproperly 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 FDA’s website at http://www.fda.gov/safesharpsdisposal.Important: Keep the sharps disposal container out of the reach of children. •Do not reuse the prefilled syringe. •Do not recycle prefilled syringes or throw them into household waste.This Instructions for Use has been approved by the U.S. Food and Drug Administration.Manufactured by:Mylan GmbHZurich, Switzerland CH-8050U.S. License No. 2062Code No.: KR/DRUGS/KTK/28D/7/2006BF1638/01Revised: 6/2018B:IFU:PEGFIL:R1BF1638/01

* Please review the disclaimer below.