ZIEXTENZO

ZIEXTENZO- pegfilgrastim injection
Sandoz Inc

1 INDICATIONS AND USAGE

1.1 Patients with Cancer Receiving Myelosuppressive Chemotherapy

ZIEXTENZO 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

ZIEXTENZO 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 ZIEXTENZO 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 ZIEXTENZO between 14 days before and 24 hours after administration of cytotoxic chemotherapy.

2.2 Administration

ZIEXTENZO is administered subcutaneously via a single-dose prefilled syringe for manual use.

Prior to use‚ remove the carton from the refrigerator and allow the ZIEXTENZO prefilled syringe to reach room temperature for a minimum of 15-30 minutes. Discard any prefilled syringe left at room temperature for greater than 120 hours.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. ZIEXTENZO is supplied as a clear and colorless to slightly yellowish solution. Do not administer ZIEXTENZO if discoloration or particulates are observed.

The needle cap on the prefilled syringes contains dry natural rubber (derived from latex) which may cause allergic reactions; persons with latex allergies should not administer these products.

Pediatric Patients weighing less than 45 kg

The ZIEXTENZO 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 ZIEXTENZO 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 ZIEXTENZO for pediatric patients weighing less than 45 kg

* For pediatric patients weighing less than 10 kg, administer 0.1 mg/kg (0.01 mL/kg) of ZIEXTENZO.
Body Weight	ZIEXTENZO Dose	Volume to Administer
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

ZIEXTENZO is a clear, colorless to slightly yellowish, preservative-free solution available as:

•

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

4 CONTRAINDICATIONS

ZIEXTENZO 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 ZIEXTENZO.

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 ZIEXTENZO, for ARDS. Discontinue ZIEXTENZO 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 ZIEXTENZO in patients with serious allergic reactions. Do not administer ZIEXTENZO 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 ZIEXTENZO if sickle cell crisis occurs.

5.5 Glomerulonephritis

Glomerulonephritis has occurred in patients receiving pegfilgrastim. 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. If glomerulonephritis is suspected, evaluate for cause. If causality is likely, consider dose-reduction or interruption of ZIEXTENZO.

5.6 Leukocytosis

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

5.7 Thrombocytopenia

Thrombocytopenia has been reported in patients receiving pegfilgrastim. Monitor platelet counts.

5.8 Capillary Leak Syndrome

Capillary leak syndrome has been reported after G-CSF administration, including pegfilgrastim, 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.