Pegfilgrastim-Apgf

FDA Drug Information • Also known as: Nyvepria

Brand Names: Nyvepria
Drug Class: Leukocyte Growth Factor [EPC]
Route: SUBCUTANEOUS
Dosage Form: INJECTION, SOLUTION
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION Pegfilgrastim-apgf 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-apgf, 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-apgf is approximately 39 kD. NYVEPRIA for manual subcutaneous injection is supplied in 0.6 mL prefilled syringes. 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 for manual subcutaneous injection contains 6 mg pegfilgrastim-apgf (based on protein weight) in a sterile, clear, colorless, preservative-free solution (pH 4.0) containing acetate (0.35 mg), polysorbate 20 (0.02 mg), sodium (0.01 mg), and sorbitol (30 mg) in Water for Injection, USP.

What Is Pegfilgrastim-Apgf Used For?

1 INDICATIONS AND USAGE NYVEPRIA 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) ] . NYVEPRIA is a 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 a clinically significant incidence of febrile neutropenia. ( 1 ) Limitations of Use NYVEPRIA is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation. ( 1 ) Limitations of Use NYVEPRIA is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Patients with cancer receiving myelosuppressive chemotherapy

6 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 NYVEPRIA 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 NYVEPRIA between 14 days before and 24 hours after administration of cytotoxic chemotherapy. 2.2 Administration NYVEPRIA is administered subcutaneously via a single-dose prefilled syringe for manual use. Prior to use‚ remove the carton from the refrigerator and allow the NYVEPRIA prefilled syringe to reach room temperature for a minimum of 30 minutes. Discard any prefilled syringe left at room temperature for greater than 15 days. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. NYVEPRIA is supplied as a clear and colorless solution. Do not administer NYVEPRIA if discoloration or particulates are observed. The NYVEPRIA syringe plunger stopper and needle cover are not made with natural rubber latex. Pediatric Patients Weighing Less than 45 kg The NYVEPRIA 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 NYVEPRIA 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 NYVEPRIA for Pediatric Patients Weighing Less than 45 kg Body Weight NYVEPRIA Dose Volume to Administer Less than 10 kg For pediatric patients weighing less than 10 kg, administer 0.1 mg/kg (0.01 mL/kg) of NYVEPRIA. See below See below 10 – 20 kg 1.5 mg 0.15 mL 21 – 30 kg 2.5 mg 0.25 mL 31 – 44 kg 4 mg 0.4 mL

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant 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) ] 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 Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. * Biosimilar means that the biological product is approved based on data demonstrating that it is highly similar to an FDA-approved biological product, known as a reference product, and that there are no clinically meaningful differences between the biosimilar product and the reference product. Biosimilarity of NYVEPRIA has been demonstrated for the condition(s) of use (e.g., indication(s), dosing regimen(s)), strength(s), dosage form(s), and route(s) of administration described in its Full Prescribing Information. 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 to rates in the clinical trials of another drug and may not reflect the rates observed in 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/m 2 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 3 Body System Adverse Reaction Placebo (N = 461) Pegfilgrastim 6 mg SC on Day 2 (N = 467) Musculoskeletal and connective tissue disorders Bone pain 26% 31% Pain in extremity 4% 9% Leukocytosis In clinical studies, leukocytosis (WBC counts >100 × 10 9 /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....

Contraindications

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

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Although available data with NYVEPRIA 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 to 4% and 15 to 20%, respectively. Data 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...

Overdosage

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) ] .

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING NYVEPRIA (pegfilgrastim-apgf) injection is a clear, colorless solution supplied in a prefilled single-dose syringe for manual use containing 6 mg pegfilgrastim-apgf, supplied with a 27-gauge 1/2-inch needle and a BD UltraSafe Plus™ Passive Needle Guard. The NYVEPRIA syringe plunger stopper and needle cover are not made with natural rubber latex. NYVEPRIA is provided in a dispensing pack containing one sterile 6 mg/0.6 mL prefilled syringe (NDC 0069-0324-01). NYVEPRIA 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 36°F to 46°F (2°C to 8°C) in the carton to protect from light. Do not shake. Discard syringes stored at room temperature for more than 15 days. Avoid freezing; if frozen, thaw in the refrigerator before administration. Discard syringe if frozen more than once.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.