NYVEPRIA

NYVEPRIA- pegfilgrastim injection, solution
Pfizer Laboratories Div Pfizer Inc

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)].

Limitations of Use

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

2 DOSAGE AND ADMINISTRATION

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
* For pediatric patients weighing less than 10 kg, administer 0.1 mg/kg (0.01 mL/kg) of NYVEPRIA.
Less than 10 kg *	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

3 DOSAGE FORMS AND STRENGTHS

NYVEPRIA is a clear, colorless, preservative-free solution available as:

•

Injection: 6 mg/0.6 mL in a single-dose prefilled syringe for manual use only.

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)].

5 WARNINGS AND PRECAUTIONS

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 NYVEPRIA.

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 NYVEPRIA, for ARDS. Discontinue NYVEPRIA 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 NYVEPRIA in patients with serious allergic reactions. Do not administer NYVEPRIA 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. Discontinue NYVEPRIA 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 NYVEPRIA.

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 NYVEPRIA 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 a 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 a 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 NYVEPRIA if aortitis is suspected.