Filgrastim (neupogen ®)

Filgrastim (Neupogen ®)

Usual Diluents

Standard Dilutions [Amount of drug] [Infusion volume] [Infusion rate]

Stability / Miscellaneous

Note: if Neupogen is diluted to a concentration below 15 mcg/ml, it should be protected from absorption to glass and plastic by the addition of albumin to a final concentration of 2 mg/ml.

ANC (absolute neutrophil count)= (% segs + % bands) x WBC.

DESCRIPTION
Filgrastim is a human granulocyte colony-stimulating factor (G-CSF)‚ produced by recombinant DNA technology. NEUPOGEN® is the Amgen Inc. trademark for Filgrastim‚ which has been selected as the name for recombinant methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF).

NEUPOGEN® is a 175 amino acid protein manufactured by recombinant DNA technology.1 NEUPOGEN® is produced by Escherichia coli (E coli) bacteria into which has been inserted the human granulocyte colony-stimulating factor gene. NEUPOGEN® has a molecular weight of 18‚800 daltons. The protein has an amino acid sequence that is identical to the natural sequence predicted from human DNA sequence analysis‚ except for the addition of an N-terminal methionine necessary for expression in E coli. Because NEUPOGEN® is produced in E coli‚ the product is nonglycosylated and thus differs from G-CSF isolated from a human cell.

NEUPOGEN® is a sterile‚ clear‚ colorless‚ preservative-free liquid for parenteral administration containing Filgrastim at a specific activity of 1.0 ± 0.6 x 10⁸ U/mg (as measured by a cell mitogenesis assay). The product is available in single use vials and prefilled syringes. The single use vials contain either 300 mcg or 480 mcg Filgrastim at a fill volume of 1.0 mL or 1.6 mL, respectively. The single use prefilled syringes contain either 300 mcg or 480 mcg Filgrastim at a fill volume of 0.5 mL or 0.8 mL, respectively.

CLINICAL PHARMACOLOGY

Colony-stimulating Factors
Colony-stimulating factors are glycoproteins which act on hematopoietic cells by binding to specific cell surface receptors and stimulating proliferation‚ differentiation commitment‚ and some end-cell functional activation.

Endogenous G-CSF is a lineage specific colony-stimulating factor which is produced by monocytes‚ fibroblasts, and endothelial cells. G-CSF regulates the production of neutrophils within the bone marrow and affects neutrophil progenitor proliferation‚ differentiation and selected end-cell functional activation (including enhanced phagocytic ability priming of the cellular metabolism associated with respiratory burst antibody dependent killing and the increased expression of some functions associated with cell surface antigens). G-CSF is not species specific and has been shown to have minimal direct in vivo or in vitro effects on the production of hematopoietic cell types other than the neutrophil lineage.

DOSAGE AND ADMINISTRATION
NEUPOGEN® is supplied in either vials or in prefilled syringes with UltraSafe® Needle Guards. Following administration of NEUPOGEN® from the prefilled syringe, the UltraSafe® Needle Guard should be activated to prevent accidental needle sticks. To activate the UltraSafe® Needle Guard, place your hands behind the needle, grasp the guard with one hand, and slide the guard forward until the needle is completely covered and the guard clicks into place. NOTE: If an audible click is not heard, the needle guard may not be completely activated. The prefilled syringe should be disposed of by placing the entire prefilled syringe with guard activated into an approved puncture-proof container.

Cancer Patients Receiving Myelosuppressive Chemotherapy
The recommended starting dose of NEUPOGEN® is 5 mcg/kg/day‚ administered as a single daily injection by SC bolus injection‚ by short IV infusion (15 to 30 minutes)‚ or by continuous SC or continuous IV infusion. A CBC and platelet count should be obtained before instituting NEUPOGEN® therapy‚ and monitored twice weekly during therapy. Doses may be increased in increments of 5 mcg/kg for each chemotherapy cycle‚ according to the duration and severity of the ANC nadir.

NEUPOGEN® should be administered no earlier than 24 hours after the administration of cytotoxic chemotherapy. NEUPOGEN® should not be administered in the period 24 hours before the administration of chemotherapy (see package insert for PRECAUTIONS). NEUPOGEN® should be administered daily for up to 2 weeks‚ until the ANC has reached 10‚000/mm3 following the expected chemotherapy-induced neutrophil nadir. The duration of NEUPOGEN® therapy needed to attenuate chemotherapy-induced neutropenia may be dependent on the myelosuppressive potential of the chemotherapy regimen employed. NEUPOGEN® therapy should be discontinued if the ANC surpasses 10‚000/mm3 after the expected chemotherapy-induced neutrophil nadir (see package insert for PRECAUTIONS). In phase 3 trials‚ efficacy was observed at doses of 4 to 8 mcg/kg/day.

Cancer Patients Receiving Bone Marrow Transplant
The recommended dose of NEUPOGEN® following BMT is 10 mcg/kg/day given as an IV infusion of 4 or 24 hours‚ or as a continuous 24-hour SC infusion. For patients receiving BMT‚ the first dose of NEUPOGEN® should be administered at least 24 hours after cytotoxic chemotherapy and at least 24 hours after bone marrow infusion.

During the period of neutrophil recovery‚ the daily dose of NEUPOGEN® should be titrated against the neutrophil response as follows:

Peripheral Blood Progenitor Cell Collection and Therapy in Cancer Patients
The recommended dose of NEUPOGEN® for the mobilization of PBPC is 10 mcg/kg/day SC‚ either as a bolus or a continuous infusion. It is recommended that NEUPOGEN® be given for at least 4 days before the first leukapheresis procedure and continued until the last leukapheresis. Although the optimal duration of NEUPOGEN® administration and leukapheresis schedule have not been established‚ administration of NEUPOGEN® for 6 to 7 days with leukaphereses on days 5‚ 6‚ and 7 was found to be safe and effective (see CLINICAL EXPERIENCE for schedules used in clinical trials). Neutrophil counts should be monitored after 4 days of NEUPOGEN®, and NEUPOGEN® dose modification should be considered for those patients who develop a WBC count > 100‚000/mm3.

In all clinical trials of NEUPOGEN® for the mobilization of PBPC‚ NEUPOGEN® was also administered after reinfusion of the collected cells (see CLINICAL EXPERIENCE).

Patients With Severe Chronic Neutropenia
NEUPOGEN® should be administered to those patients in whom a diagnosis of congenital‚ cyclic‚ or idiopathic neutropenia has been definitively confirmed. Other diseases associated with neutropenia should be ruled out.

Starting Dose:

Congenital Neutropenia: The recommended daily starting dose is 6 mcg/kg BID SC every day.

Idiopathic or Cyclic Neutropenia: The recommended daily starting dose is 5 mcg/kg as a single injection SC every day.

Dose Adjustments:

Chronic daily administration is required to maintain clinical benefit. Absolute neutrophil count should not be used as the sole indication of efficacy. The dose should be individually adjusted based on the patients’ clinical course as well as ANC. In the SCN postmarketing surveillance study, the reported median daily doses of NEUPOGEN® were: 6.0 mcg/kg (congenital neutropenia), 2.1 mcg/kg (cyclic neutropenia), and 1.2 mcg/kg (idiopathic neutropenia). In rare instances, patients with congenital neutropenia have required doses of NEUPOGEN® ≥ 100 mcg/kg/day.

Dilution
If required‚ NEUPOGEN® may be diluted in 5% dextrose. NEUPOGEN® diluted to concentrations between 5 and 15 mcg/mL should be protected from adsorption to plastic materials by the addition of Albumin (Human) to a final concentration of 2 mg/mL. When diluted in 5% dextrose or 5% dextrose plus Albumin (Human)‚ NEUPOGEN® is compatible with glass bottles‚ PVC and polyolefin IV bags‚ and polypropylene syringes.

Dilution of NEUPOGEN® to a final concentration of less than 5 mcg/mL is not recommended at any time. Do not dilute with saline at any time; product may precipitate.

Storage
NEUPOGEN® should be stored in the refrigerator at 2° to 8°C (36° to 46°F). Avoid shaking. Prior to injection‚ NEUPOGEN® may be allowed to reach room temperature for a maximum of 24 hours. Any vial or prefilled syringe left at room temperature for greater than 24 hours should be discarded. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration‚ whenever solution and container permit; if particulates or discoloration are observed‚ the container should not be used.

HOW SUPPLIED
NEUPOGEN®: Use only one dose per vial; do not re-enter the vial. Discard unused portions. Do not save unused drug for later administration.

Use only one dose per prefilled syringe. Discard unused portions. Do not save unused drug for later administration.

Vials
Single-dose‚ preservative-free vials containing 300 mcg (1 mL) of Filgrastim (300 mcg/mL). Dispensing packs of 10 (NDC 55513-530-10).

Single-dose‚ preservative-free vials containing 480 mcg (1.6 mL) of Filgrastim (300 mcg/mL). Dispensing packs of 10 (NDC 55513-546-10).

Prefilled Syringes (SingleJect®)
Single-dose‚ preservative-free, prefilled syringes with 27 gauge, ½ inch needles with an UltraSafe® Needle Guard, containing 300 mcg (0.5 mL) of Filgrastim (600 mcg/mL). Dispensing packs of 10 (NDC 55513-924-10).

Single-dose‚ preservative-free, prefilled syringes with 27 gauge, ½ inch needles with an UltraSafe® Needle Guard, containing 480 mcg (0.8 mL) of Filgrastim (600 mcg/mL). Dispensing packs of 10 (NDC 55513-209-10).

The needle cover of the prefilled syringe contains dry natural rubber (a derivative of latex).

NEUPOGEN® should be stored at 2° to 8°C (36° to 46°F). Avoid shaking.