Filgrastim

Filgrastim
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]

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Overview

Filgrastim is a human granulocyte colony-stimulating factor that is FDA approved for the treatment of Cancer Patients Receiving Myelosuppressive Chemotherapy， Patients With Acute Myeloid Leukemia Receiving Induction or Consolidation Chemotherapy， Cancer Patients Receiving Bone Marrow Transplant， Patients Undergoing Peripheral Blood Progenitor Cell Collection and Therapy， Patients With Severe Chronic Neutropenia. Common adverse reactions include Bone pain.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Cancer Patients Receiving Myelosuppressive Chemotherapy

• Dosing information

• Recommended starting dosage: 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.
• 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.

Cancer Patients Receiving Bone Marrow Transplant

• Dosing information

• Recommended dosage following BMT: 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:

This image is provided by the National Library of Medicine.

Peripheral Blood Progenitor Cell Collection and Therapy in Cancer Patients

• Dosing information

• Recommended dosage for the mobilization of PBPC: 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. 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.

Patients With Severe Chronic Neutropenia

• Dosing information

• 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 injection SC qd.

• 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 patient's 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.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Myelodysplastic syndrome

• Developed by: American Society of Clinical Oncology (ASCO)

• Class of Recommendation: Not applicable

• Level of Evidence: Not applicable

• Dosing Information

• Intermittent CSF use may be considered in patients with severe neutropenia and recurrent infections.

Cancer Patients Receiving Myelosuppressive Chemotherapy

• Dosing information

• Recommended starting dosage: 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.
• 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.

Non–Guideline-Supported Use

Agranulocytosis

• Dosing information

• 350 micrograms/day 7507240
• 5 micrograms/kg/day subcutaneously for 7 days 7512460
• 300 micrograms/day subcutaneously7525175

Aplastic anemia

• Dosing information

• 20 milligrams/kilogram/day (mg/kg/day)

Disorder related to renal transplantation - Neutropenic disorder

• Dosing information

• 6 micrograms/kilogram/day subcutaneously 12803133

Febrile neutropenia

• Dosing information

• 100mcg/m(2) to 400 mcg/m(2) 10071455

Infectious disease

• Dosing information

• 300 micrograms/day (mcg/day) subcutaneously to 480 mcg/day10803937

Leukemia

• Dosing information

• 5 micrograms/kilogram/day11426551

Mucositis following chemotherapy

• Dosing information

• 120 mcg (0.4 mL)9827976

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Cancer Patients Receiving Myelosuppressive Chemotherapy

• Dosing information

• Recommended starting dosage: 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.
• 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.

Cancer Patients Receiving Bone Marrow Transplant

• Dosing information

• Recommended dosage following BMT: 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:

This image is provided by the National Library of Medicine.

Peripheral Blood Progenitor Cell Collection and Therapy in Cancer Patients

• Dosing information

• Recommended dosage for the mobilization of PBPC: 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. 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.

Patients With Severe Chronic Neutropenia

• Dosing information

• 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 injection SC qd.

• 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 patient's 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.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Filgrastim in pediatric patients.

Non–Guideline-Supported Use

Aplastic anemia

• Dosing information

• Not applicable 10979946

Neutropenia - Pre-eclampsia

• Dosing information

• 5 or 10 micrograms/kilogram (mcg/kg)/day9794941

Septicemia of newborn

• Dosing information

• Not applicable 11391341

Shwachman syndrome

• Dosing information

• Not applicable 1700246

Contraindications

NEUPOGEN® is contraindicated in patients with known hypersensitivity to E coli-derived proteins‚ filgrastim‚ or any component of the product.

Warnings

Allergic Reactions

Allergic-type reactions occurring on initial or subsequent treatment have been reported in < 1 in 4000 patients treated with NEUPOGEN®. These have generally been characterized by systemic symptoms involving at least two body systems‚ most often skin (rash‚ urticaria‚ facial edema)‚ respiratory (wheezing‚ dyspnea)‚ and cardiovascular (hypotension‚ tachycardia). Some reactions occurred on initial exposure. Reactions tended to occur within the first 30 minutes after administration and appeared to occur more frequently in patients receiving NEUPOGEN® IV. Rapid resolution of symptoms occurred in most cases after administration of antihistamines‚ steroids‚ bronchodilators‚ and/or epinephrine. Symptoms recurred in more than half the patients who were rechallenged.

SPLENIC RUPTURE

SPLENIC RUPTURE, INCLUDING FATAL CASES, HAS BEEN REPORTED FOLLOWING THE ADMINISTRATION OF NEUPOGEN®. INDIVIDUALS RECEIVING NEUPOGEN® WHO REPORT LEFT UPPER ABDOMINAL AND/OR SHOULDER TIP PAIN SHOULD BE EVALUATED FOR AN ENLARGED SPLEEN OR SPLENIC RUPTURE.

Acute Respiratory Distress Syndrome (ARDS)

Acute respiratory distress syndrome (ARDS) has been reported in patients receiving NEUPOGEN®, and is postulated to be secondary to an influx of neutrophils to sites of inflammation in the lungs. Patients receiving NEUPOGEN® who develop fever, lung infiltrates, or respiratory distress should be evaluated for the possibility of ARDS. In the event that ARDS occurs, NEUPOGEN® should be withheld until resolution of ARDS or discontinued. Patients should receive appropriate medical management for this condition.

Alveolar Hemorrhage and Hemoptysis

Alveolar hemorrhage manifesting as pulmonary infiltrates and hemoptysis requiring hospitalization has been reported in healthy donors undergoing PBPC mobilization. Hemoptysis resolved with discontinuation of NEUPOGEN®. The use of NEUPOGEN® for PBPC mobilization in healthy donors is not an approved indication.

Sickle Cell Disorders

Severe sickle cell crises, in some cases resulting in death, have been associated with the use of NEUPOGEN® in patients with sickle cell disorders. Only physicians qualified by specialized training or experience in the treatment of patients with sickle cell disorders should prescribe NEUPOGEN® for such patients, and only after careful consideration of the potential risks and benefits.

Patients With Severe Chronic Neutropenia

The safety and efficacy of NEUPOGEN® in the treatment of neutropenia due to other hematopoietic disorders (eg‚ myelodysplastic syndrome [MDS]) have not been established. Care should be taken to confirm the diagnosis of SCN before initiating NEUPOGEN® therapy. MDS and AML have been reported to occur in the natural history of congenital neutropenia without cytokine therapy.17 Cytogenetic abnormalities, transformation to MDS, and AML have also been observed in patients treated with NEUPOGEN® for SCN. Based on available data including a postmarketing surveillance study, the risk of developing MDS and AML appears to be confined to the subset of patients with congenital neutropenia. Abnormal cytogenetics and MDS have been associated with the eventual development of myeloid leukemia. The effect of NEUPOGEN® on the development of abnormal cytogenetics and the effect of continued NEUPOGEN® administration in patients with abnormal cytogenetics or MDS are unknown. If a patient with SCN develops abnormal cytogenetics or myelodysplasia‚ the risks and benefits of continuing NEUPOGEN® should be carefully considered.

PRECAUTIONS

General

Simultaneous Use With Chemotherapy and Radiation Therapy

The safety and efficacy of NEUPOGEN® given simultaneously with cytotoxic chemotherapy have not been established. Because of the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy‚ do not use NEUPOGEN® in the period 24 hours before through 24 hours after the administration of cytotoxic chemotherapy (see DOSAGE AND ADMINISTRATION). The efficacy of NEUPOGEN® has not been evaluated in patients receiving chemotherapy associated with delayed myelosuppression (e.g., nitrosoureas), with mitomycin C, or with myelosuppressive doses of antimetabolites such as 5-fluorouracil. The safety and efficacy of NEUPOGEN® have not been evaluated in patients receiving concurrent radiation therapy. Simultaneous use of NEUPOGEN® with chemotherapy and radiation therapy should be avoided.

Potential Effect on Malignant Cells

NEUPOGEN® is a growth factor that primarily stimulates neutrophils. However‚ the possibility that NEUPOGEN® can act as a growth factor for any tumor type cannot be excluded. In a randomized study evaluating the effects of NEUPOGEN® versus placebo in patients undergoing remission induction for AML, there was no significant difference in remission rate, disease-free, or overall survival (see CLINICAL EXPERIENCE). The safety of NEUPOGEN® in chronic myeloid leukemia (CML) and myelodysplasia has not been established. When NEUPOGEN® is used to mobilize PBPC‚ tumor cells may be released from the marrow and subsequently collected in the leukapheresis product. The effect of reinfusion of tumor cells has not been well studied‚ and the limited data available are inconclusive.

Leukocytosis

Cancer Patients Receiving Myelosuppressive Chemotherapy

White blood cell counts of 100‚000/mm3 or greater were observed in approximately 2% of patients receiving NEUPOGEN® at doses above 5 mcg/kg/day. There were no reports of adverse events associated with this degree of leukocytosis. In order to avoid the potential complications of excessive leukocytosis‚ a CBC is recommended twice per week during NEUPOGEN® therapy (see LABORATORY MONITORING).

Premature Discontinuation of NEUPOGEN® Therapy

Cancer Patients Receiving Myelosuppressive Chemotherapy

A transient increase in neutrophil counts is typically seen 1 to 2 days after initiation of NEUPOGEN® therapy. However‚ for a sustained therapeutic response‚ NEUPOGEN® therapy should be continued following chemotherapy until the post-nadir ANC reaches 10‚000/mm3. Therefore‚ the premature discontinuation of NEUPOGEN® therapy‚ prior to the time of recovery from the expected neutrophil nadir‚ is generally not recommended (see DOSAGE AND ADMINISTRATION).

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. The incidence of antibody development in patients receiving NEUPOGEN® has not been adequately determined. While available data suggest that a small proportion of patients developed binding antibodies to filgrastim, the nature and specificity of these antibodies has not been adequately studied. In clinical studies comparing NEUPOGEN® and Neulasta®, the incidence of antibodies binding to NEUPOGEN® was 3% (11/333). In these 11 patients, no evidence of a neutralizing response was observed using a cell-based bioassay. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay, and the observed incidence of antibody positivity in an assay may be influenced by several factors including timing of sampling, sample handling, concomitant medications, and underlying disease. Therefore, comparison of the incidence of antibodies to NEUPOGEN® with the incidence of antibodies to other products may be misleading. Cytopenias resulting from an antibody response to exogenous growth factors have been reported on rare occasions in patients treated with other recombinant growth factors. There is a theoretical possibility that an antibody directed against filgrastim may cross-react with endogenous G-CSF, resulting in immune-mediated neutropenia; however, this has not been reported in clinical studies or in post-marketing experience. Patients who develop hypersensitivity to filgrastim (NEUPOGEN®) may have allergic or hypersensitivity reactions to other E coli-derived proteins.

Cutaneous Vasculitis

Cutaneous vasculitis has been reported in patients treated with NEUPOGEN®. In most cases‚ the severity of cutaneous vasculitis was moderate or severe. Most of the reports involved patients with SCN receiving long-term NEUPOGEN® therapy. Symptoms of vasculitis generally developed simultaneously with an increase in the ANC and abated when the ANC decreased. Many patients were able to continue NEUPOGEN® at a reduced dose.

Thrombocytopenia

Thrombocytopenia has been reported in patients receiving NEUPOGEN®.  Platelet counts should be monitored closely.

Information for Patients and Caregivers

Patients should be referred to the “Information for Patients and Caregivers” labeling included with the package insert in each dispensing pack of NEUPOGEN® vials or NEUPOGEN® prefilled syringes. The “Information for Patients and Caregivers” labeling provides information about neutrophils and neutropenia and the safety and efficacy of NEUPOGEN®. It is not intended to be a disclosure of all known or possible effects.

Laboratory Monitoring

Cancer Patients Receiving Myelosuppressive Chemotherapy

A CBC and platelet count should be obtained prior to chemotherapy‚ and at regular intervals (twice per week) during NEUPOGEN® therapy. Following cytotoxic chemotherapy‚ the neutrophil nadir occurred earlier during cycles when NEUPOGEN® was administered‚ and WBC differentials demonstrated a left shift‚ including the appearance of promyelocytes and myeloblasts. In addition‚ the duration of severe neutropenia was reduced and was followed by an accelerated recovery in the neutrophil counts.

Cancer Patients Receiving Bone Marrow Transplant

Frequent CBCs and platelet counts are recommended (at least 3 times per week) following marrow transplantation.

Patients With Severe Chronic Neutropenia

During the initial 4 weeks of NEUPOGEN® therapy and during the 2 weeks following any dose adjustment‚ a CBC with differential and platelet count should be performed twice weekly. Once a patient is clinically stable‚ a CBC with differential and platelet count should be performed monthly during the first year of treatment. Thereafter, if clinically stable, routine monitoring with regular CBCs (i.e., as clinically indicated but at least quarterly) is recommended. Additionally, for those patients with congenital neutropenia, annual bone marrow and cytogenetic evaluations should be performed throughout the duration of treatment. In clinical trials‚ the following laboratory results were observed:

• Cyclic fluctuations in the neutrophil counts were frequently observed in patients with congenital or idiopathic neutropenia after initiation of NEUPOGEN® therapy.
• Platelet counts were generally at the upper limits of normal prior to NEUPOGEN® therapy. With NEUPOGEN® therapy‚ platelet counts decreased but usually remained within normal limits (see ADVERSE REACTIONS).
• Early myeloid forms were noted in peripheral blood in most patients‚ including the appearance of metamyelocytes and myelocytes. Promyelocytes and myeloblasts were noted in some patients.
• Relative increases were occasionally noted in the number of circulating eosinophils and basophils. No consistent increases were observed with NEUPOGEN® therapy.
• As in other trials‚ increases were observed in serum uric acid‚ lactic dehydrogenase‚ and serum alkaline phosphatase.

Adverse Reactions

Clinical Trials Experience

Clinical Trial Experience

Cancer Patients Receiving Myelosuppressive Chemotherapy

In clinical trials involving over 350 patients receiving NEUPOGEN® following nonmyeloablative cytotoxic chemotherapy‚ most adverse experiences were the sequelae of the underlying malignancy or cytotoxic chemotherapy. In all phase 2 and 3 trials‚ medullary bone pain‚ reported in 24% of patients‚ was the only consistently observed adverse reaction attributed to NEUPOGEN® therapy. This bone pain was generally reported to be of mild-to-moderate severity‚ and could be controlled in most patients with non-narcotic analgesics; infrequently‚ bone pain was severe enough to require narcotic analgesics. Bone pain was reported more frequently in patients treated with higher doses (20 to 100 mcg/kg/day) administered IV‚ and less frequently in patients treated with lower SC doses of NEUPOGEN® (3 to 10 mcg/kg/day). In the randomized‚ double-blind‚ placebo-controlled trial of NEUPOGEN® therapy following combination chemotherapy in patients (n = 207) with small cell lung cancer‚ the following adverse events were reported during blinded cycles of study medication (placebo or NEUPOGEN® at 4 to 8 mcg/kg/day). Events are reported as exposure-adjusted since patients remained on double-blind NEUPOGEN® a median of 3 cycles versus 1 cycle for placebo.

This image is provided by the National Library of Medicine.

In this study‚ there were no serious‚ life-threatening‚ or fatal adverse reactions attributed to NEUPOGEN® therapy. Specifically‚ there were no reports of flu-like symptoms‚ pleuritis‚ pericarditis‚ or other major systemic reactions to NEUPOGEN®. Spontaneously reversible elevations in uric acid‚ lactate dehydrogenase‚ and alkaline phosphatase occurred in 27% to 58% of 98 patients receiving blinded NEUPOGEN® therapy following cytotoxic chemotherapy; increases were generally mild-to-moderate. Transient decreases in blood pressure (< 90/60 mmHg)‚ which did not require clinical treatment‚ were reported in 7 of 176 patients in phase 3 clinical studies following administration of NEUPOGEN®. Cardiac events (myocardial infarctions‚ arrhythmias) have been reported in 11 of 375 cancer patients receiving NEUPOGEN® in clinical studies; the relationship to NEUPOGEN® therapy is unknown. No evidence of interaction of NEUPOGEN® with other drugs was observed in the course of clinical trials (see PRECAUTIONS). There has been no evidence for the development of antibodies or of a blunted or diminished response to NEUPOGEN® in treated patients‚ including those receiving NEUPOGEN® daily for almost 2 years.

Patients With Acute Myeloid Leukemia

In a randomized phase 3 clinical trial, 259 patients received NEUPOGEN® and 262 patients received placebo postchemotherapy. Overall, the frequency of all reported adverse events was similar in both the NEUPOGEN® and placebo groups (83% vs 82% in Induction 1; 61% vs 64% in Consolidation 1). Adverse events reported more frequently in the NEUPOGEN®-treated group included: petechiae (17% vs 14%), epistaxis (9% vs 5%), and transfusion reactions (10% vs 5%). There were no significant differences in the frequency of these events. There were a similar number of deaths in each treatment group during induction (25 NEUPOGEN® vs 27 placebo). The primary causes of death included infection (9 vs 18), persistent leukemia (7 vs 5), and hemorrhage (6 vs 3). Of the hemorrhagic deaths, 5 cerebral hemorrhages were reported in the NEUPOGEN® group and 1 in the placebo group. Other serious nonfatal hemorrhagic events were reported in the respiratory tract (4 vs 1), skin (4 vs 4), gastrointestinal tract (2 vs 2), urinary tract (1 vs 1), ocular (1 vs 0), and other nonspecific sites (2 vs 1). While 19 (7%) patients in the NEUPOGEN® group and 5 (2%) patients in the placebo group experienced severe or fatal hemorrhagic events, overall, hemorrhagic adverse events were reported at a similar frequency in both groups (40% vs 38%). The time to transfusion-independent platelet recovery and the number of days of platelet transfusions were similar in both groups.

Cancer Patients Receiving Bone Marrow Transplant

In clinical trials‚ the reported adverse effects were those typically seen in patients receiving intensive chemotherapy followed by BMT. The most common events reported in both control and treatment groups included stomatitis, nausea, and vomiting‚ generally of mild-to-moderate severity and were considered unrelated to NEUPOGEN®. In the randomized studies of BMT involving 167 patients who received study drug‚ the following events occurred more frequently in patients treated with filgrastim than in controls: nausea (10% vs 4%)‚ vomiting (7% vs 3%)‚ hypertension (4% vs 0%)‚ rash (12% vs 10%)‚ and peritonitis (2% vs 0%). None of these events were reported by the investigator to be related to NEUPOGEN®. One event of erythema nodosum was reported moderate in severity and possibly related to NEUPOGEN®. Generally‚ adverse events observed in nonrandomized studies were similar to those seen in randomized studies‚ occurred in a minority of patients and were of mild-to-moderate severity. In one study (n = 45)‚ 3 serious adverse events reported by the investigator were considered possibly related to NEUPOGEN®. These included 2 events of renal insufficiency and 1 event of capillary leak syndrome. The relationship of these events to NEUPOGEN® remains unclear since they occurred in patients with culture-proven infection with clinical sepsis who were receiving potentially nephrotoxic antibacterial and antifungal therapy.

Cancer Patients Undergoing Peripheral Blood Progenitor Cell Collection and Therapy

In clinical trials‚ 126 patients received NEUPOGEN® for PBPC mobilization. In this setting‚ NEUPOGEN® was generally well tolerated. Adverse events related to NEUPOGEN® consisted primarily of mild-to-moderate musculoskeletal symptoms‚ reported in 44% of patients. These symptoms were predominantly events of medullary bone pain (33%). Headache was reported related to NEUPOGEN® in 7% of patients. Transient increases in alkaline phosphatase related to NEUPOGEN® were reported in 21% of the patients who had serum chemistries measured; most were mild-to-moderate. All patients had increases in neutrophil counts during mobilization‚ consistent with the biological effects of NEUPOGEN®. Two patients had a WBC count > 100‚000/mm3. No sequelae were associated with any grade of leukocytosis. Sixty-five percent of patients had mild-to-moderate anemia and 97% of patients had decreases in platelet counts; 5 patients (out of 126) had decreased platelet counts to < 50‚000/mm3. Anemia and thrombocytopenia have been reported to be related to leukapheresis; however‚ the possibility that NEUPOGEN® mobilization may contribute to anemia or thrombocytopenia has not been ruled out.

Patients With Severe Chronic Neutropenia

Mild-to-moderate bone pain was reported in approximately 33% of patients in clinical trials. This symptom was readily controlled with non-narcotic analgesics. Generalized musculoskeletal pain was also noted in higher frequency in patients treated with NEUPOGEN®. Palpable splenomegaly was observed in approximately 30% of patients. Abdominal or flank pain was seen infrequently, and thrombocytopenia (< 50‚000/mm3) was noted in 12% of patients with palpable spleens. Fewer than 3% of all patients underwent splenectomy‚ and most of these had a prestudy history of splenomegaly. Fewer than 6% of patients had thrombocytopenia (< 50‚000/mm3) during NEUPOGEN® therapy‚ most of whom had a pre-existing history of thrombocytopenia. In most cases‚ thrombocytopenia was managed by NEUPOGEN® dose reduction or interruption. An additional 5% of patients had platelet counts between 50‚000 and 100‚000/mm3. There were no associated serious hemorrhagic sequelae in these patients. Epistaxis was noted in 15% of patients treated with NEUPOGEN®, but was associated with thrombocytopenia in 2% of patients. Anemia was reported in approximately 10% of patients‚ but in most cases appeared to be related to frequent diagnostic phlebotomy‚ chronic illness, or concomitant medications. Other adverse events infrequently observed and possibly related to NEUPOGEN® therapy were: injection site reaction‚ rash‚ hepatomegaly‚ arthralgia‚ osteoporosis‚ cutaneous vasculitis‚ hematuria/proteinuria‚ alopecia‚ and exacerbation of some pre-existing skin disorders (e.g.‚ psoriasis). Cytogenetic abnormalities, transformation to MDS, and AML have been observed in patients treated with NEUPOGEN® for SCN (see WARNINGS, PRECAUTIONS: Pediatric Use). As of 31 December 1997, data were available from a postmarketing surveillance study of 531 SCN patients with an average follow-up of 4.0 years. Based on analysis of these data, the risk of developing MDS and AML appears to be confined to the subset of patients with congenital neutropenia. A life-table analysis of these data revealed that the cumulative risk of developing leukemia or MDS by the end of the 8th year of NEUPOGEN® treatment in a patient with congenital neutropenia was 16.5% (95% C.I. = 9.8%, 23.3%); this represents an annual rate of approximately 2%. Cytogenetic abnormalities, most commonly involving chromosome 7, have been reported in patients treated with NEUPOGEN® who had previously documented normal cytogenetics. It is unknown whether the development of cytogenetic abnormalities, MDS, or AML is related to chronic daily NEUPOGEN® administration or to the natural history of congenital neutropenia. It is also unknown if the rate of conversion in patients who have not received NEUPOGEN® is different from that of patients who have received NEUPOGEN®. Routine monitoring through regular CBCs is recommended for all SCN patients. Additionally, annual bone marrow and cytogenetic evaluations are recommended in all patients with congenital neutropenia

Postmarketing Experience

The following adverse reactions have been identified during postapproval of NEUPOGEN®. 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: Splenic Rupture)
• acute respiratory distress syndrome (ARDS) (see WARNINGS: Acute Respiratory Distress Syndrome)
• alveolar hemorrhage and hemoptysis (see WARNINGS: Alveolar Hemorrhage and Hemoptysis)
• sickle cell crisis (see WARNINGS: Sickle Cell Disorders)
• cutaneous vasculitis (see PRECAUTIONS: Cutaneous Vasculitis)
• Sweet’s syndrome (acute febrile neutrophilic dermatosis)
• decreased bone density and osteoporosis in pediatric SCN patients receiving chronic treatment with NEUPOGEN®

Drug Interactions

Drug interactions between NEUPOGEN® and other drugs have not been fully evaluated. Drugs which may potentiate the release of neutrophils‚ such as lithium‚ should be used with caution. Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone-imaging changes. This should be considered when interpreting bone-imaging results.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C NEUPOGEN® has been shown to have adverse effects in pregnant rabbits when given in doses 2 to 10 times the human dose. Since there are no adequate and well-controlled studies in pregnant women, the effect, if any, of NEUPOGEN® on the developing fetus or the reproductive capacity of the mother is unknown. However, the scientific literature describes transplacental passage of NEUPOGEN® when administered to pregnant rats during the latter part of gestation18 and apparent transplacental passage of NEUPOGEN® when administered to pregnant humans by ≤ 30 hours prior to preterm delivery (≤ 30 weeks gestation).19 NEUPOGEN® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In rabbits‚ increased abortion and embryolethality were observed in animals treated with NEUPOGEN® at 80 mcg/kg/day. NEUPOGEN® administered to pregnant rabbits at doses of 80 mcg/kg/day during the period of organogenesis was associated with increased fetal resorption‚ genitourinary bleeding‚ developmental abnormalities‚ decreased body weight‚ live births‚ and food consumption. External abnormalities were not observed in the fetuses of dams treated at 80 mcg/kg/day. Reproductive studies in pregnant rats have shown that NEUPOGEN® was not associated with lethal‚ teratogenic‚ or behavioral effects on fetuses when administered by daily IV injection during the period of organogenesis at dose levels up to 575 mcg/kg/day. In Segment III studies in rats‚ offspring of dams treated at > 20 mcg/kg/day exhibited a delay in external differentiation (detachment of auricles and descent of testes) and slight growth retardation‚ possibly due to lower body weight of females during rearing and nursing. Offspring of dams treated at 100 mcg/kg/day exhibited decreased body weights at birth‚ and a slightly reduced 4-day survival rate. Encourage women who become pregnant during NEUPOGEN® treatment to enroll in Amgen’s Pregnancy Surveillance Program. Patients or their physicians should call 1-800-77-AMGEN (1-800-772-6436) to enroll.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Filgrastim in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Filgrastim during labor and delivery.

Nursing Mothers

It is not known whether NEUPOGEN® is excreted in human milk. Because many drugs are excreted in human milk‚ caution should be exercised if NEUPOGEN® is administered to a nursing woman. Encourage women who are nursing during NEUPOGEN® treatment to enroll in Amgen’s Lactation Surveillance Program. Patients or their physicians should call 1‑800‑77‑AMGEN (1-800-772-6436) to enroll.

Pediatric Use

In a phase 3 study to assess the safety and efficacy of NEUPOGEN® in the treatment of SCN, 120 patients with a median age of 12 years were studied. Of the 120 patients, 12 were infants (1 month to 2 years of age), 47 were children (2 to 12 years of age), and 9 were adolescents (12 to 16 years of age). Additional information is available from a SCN postmarketing surveillance study, which includes long-term follow-up of patients in the clinical studies and information from additional patients who entered directly into the postmarketing surveillance study. Of the 531 patients in the surveillance study as of 31 December 1997, 32 were infants, 200 were children, and 68 were adolescents (see CLINICAL EXPERIENCE, INDICATIONS AND USAGE, LABORATORY MONITORING, and DOSAGE AND ADMINISTRATION). Pediatric patients with congenital types of neutropenia (Kostmann’s syndrome, congenital agranulocytosis, or Schwachman-Diamond syndrome) have developed cytogenetic abnormalities and have undergone transformation to MDS and AML while receiving chronic NEUPOGEN® treatment. The relationship of these events to NEUPOGEN® administration is unknown (see WARNINGS and ADVERSE REACTIONS). Long-term follow-up data from the postmarketing surveillance study suggest that height and weight are not adversely affected in patients who received up to 5 years of NEUPOGEN® treatment. Limited data from patients who were followed in the phase 3 study for 1.5 years did not suggest alterations in sexual maturation or endocrine function. The safety and efficacy in neonates and patients with autoimmune neutropenia of infancy have not been established. In the cancer setting‚ 12 pediatric patients with neuroblastoma have received up to 6 cycles of cyclophosphamide‚ cisplatin‚ doxorubicin‚ and etoposide chemotherapy concurrently with NEUPOGEN®; in this population‚ NEUPOGEN® was well tolerated. There was one report of palpable splenomegaly associated with NEUPOGEN® therapy; however‚ the only consistently reported adverse event was musculoskeletal pain‚ which is no different from the experience in the adult population.

Geriatic Use

Among 855 subjects enrolled in 3 randomized, placebo-controlled trials of NEUPOGEN® use following myelosuppressive chemotherapy, there were 232 subjects age 65 or older, and 22 subjects age 75 or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other clinical experience has not identified differences in the responses between elderly and younger patients. Clinical studies of NEUPOGEN® in other approved indications (ie, bone marrow transplant (BMT) recipients, PBPC mobilization, and SCN) did not include sufficient numbers of subjects aged 65 and older to determine whether elderly subjects respond differently from younger subjects.

Gender

There is no FDA guidance on the use of Filgrastim with respect to specific gender populations.

Race

There is no FDA guidance on the use of Filgrastim with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Filgrastim in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Filgrastim in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Filgrastim in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Filgrastim in patients who are immunocompromised.

Administration and Monitoring

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.

Monitoring

There is limited information regarding Filgrastim Monitoring in the drug label.

IV Compatibility

There is limited information about the IV Compatibility.

Overdosage

In cancer patients receiving NEUPOGEN® as an adjunct to myelosuppressive chemotherapy‚ it is recommended to avoid the potential risks of excessive leukocytosis‚ that NEUPOGEN® therapy be discontinued if the ANC surpasses 10‚000/mm3 after the chemotherapy-induced ANC nadir has occurred. Doses of NEUPOGEN® that increase the ANC beyond 10‚000/mm3 may not result in any additional clinical benefit. The maximum tolerated dose of NEUPOGEN® has not been determined. Efficacy was demonstrated at doses of 4 to 8 mcg/kg/day in the phase 3 study of nonmyeloablative chemotherapy. Patients in the BMT studies received up to 138 mcg/kg/day without toxic effects‚ although there was a flattening of the dose response curve above daily doses of greater than 10 mcg/kg/day. In NEUPOGEN® clinical trials of cancer patients receiving myelosuppressive chemotherapy‚ WBC counts > 100‚000/mm3 have been reported in less than 5% of patients‚ but were not associated with any reported adverse clinical effects. In cancer patients receiving myelosuppressive chemotherapy‚ discontinuation of NEUPOGEN® therapy usually results in a 50% decrease in circulating neutrophils within 1 to 2 days‚ with a return to pretreatment levels in 1 to 7 days.

Pharmacology

Mechanism of Action

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‚2‚3 differentiation,2‚4 and selected end-cell functional activation (including enhanced phagocytic ability‚5 priming of the cellular metabolism associated with respiratory burst‚6 antibody dependent killing,7 and the increased expression of some functions associated with cell surface antigens8). 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.

Structure

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. See table below for product composition of each single-use vial or prefilled syringe.

This image is provided by the National Library of Medicine.

Pharmacodynamics

In phase 1 studies involving 96 patients with various nonmyeloid malignancies‚ NEUPOGEN® administration resulted in a dose-dependent increase in circulating neutrophil counts over the dose range of 1 to 70 mcg/kg/day.9-11 This increase in neutrophil counts was observed whether NEUPOGEN® was administered IV (1 to 70 mcg/kg twice daily)‚9 SC (1 to 3 mcg/kg once daily)‚11 or by continuous SC infusion (3 to 11 mcg/kg/day).10 With discontinuation of NEUPOGEN® therapy‚ neutrophil counts returned to baseline in most cases within 4 days. Isolated neutrophils displayed normal phagocytic (measured by zymosan-stimulated chemoluminescence) and chemotactic (measured by migration under agarose using N-formyl-methionyl-leucyl-phenylalanine [fMLP] as the chemotaxin) activity in vitro. The absolute monocyte count was reported to increase in a dose-dependent manner in most patients receiving NEUPOGEN®; however‚ the percentage of monocytes in the differential count remained within the normal range. In all studies to date‚ absolute counts of both eosinophils and basophils did not change and were within the normal range following administration of NEUPOGEN®. Increases in lymphocyte counts following NEUPOGEN® administration have been reported in some normal subjects and cancer patients. White blood cell (WBC) differentials obtained during clinical trials have demonstrated a shift towards earlier granulocyte progenitor cells (left shift)‚ including the appearance of promyelocytes and myeloblasts‚ usually during neutrophil recovery following the chemotherapy-induced nadir. In addition‚ Dohle bodies‚ increased granulocyte granulation‚ and hypersegmented neutrophils have been observed. Such changes were transient and were not associated with clinical sequelae, nor were they necessarily associated with infection.

Pharmacokinetics

Absorption and clearance of NEUPOGEN® follows first-order pharmacokinetic modeling without apparent concentration dependence. A positive linear correlation occurred between the parenteral dose and both the serum concentration and area-under-the-concentration-time curves. Continuous IV infusion of 20 mcg/kg of NEUPOGEN® over 24 hours resulted in mean and median serum concentrations of approximately 48 and 56 ng/mL‚ respectively. Subcutaneous administration of 3.45 mcg/kg and 11.5 mcg/kg resulted in maximum serum concentrations of 4 and 49 ng/mL‚ respectively‚ within 2 to 8 hours. The volume of distribution averaged 150 mL/kg in both normal subjects and cancer patients. The elimination half-life‚ in both normal subjects and cancer patients‚ was approximately 3.5 hours. Clearance rates of NEUPOGEN® were approximately 0.5 to 0.7 mL/minute/kg. Single parenteral doses or daily IV doses‚ over a 14-day period‚ resulted in comparable half-lives. The half-lives were similar for IV administration (231 minutes‚ following doses of 34.5 mcg/kg) and for SC administration (210 minutes‚ following NEUPOGEN® doses of 3.45 mcg/kg). Continuous 24-hour IV infusions of 20 mcg/kg over an 11- to 20-day period produced steady-state serum concentrations of NEUPOGEN® with no evidence of drug accumulation over the time period investigated. Pharmacokinetic data in geriatric patients (≥ 65 years) are not available.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

The carcinogenic potential of NEUPOGEN® has not been studied. NEUPOGEN® failed to induce bacterial gene mutations in either the presence or absence of a drug metabolizing enzyme system. NEUPOGEN® had no observed effect on the fertility of male or female rats‚ or on gestation at doses up to 500 mcg/kg.

Clinical Studies

FDA Package Insert for Filgrastim contains no information regarding Clinical Studies.

How Supplied

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 syringe with 27 gauge, ½ inch needle with an UltraSafe® Needle Guard, containing 300 mcg (0.5 mL) of filgrastim (600 mcg/mL). Dispensing packs of 1 (NDC 55513-924-91). 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 syringe with 27 gauge, ½ inch needle with an UltraSafe® Needle Guard, containing 480 mcg (0.8 mL) of filgrastim (600 mcg/mL). Dispensing packs of 1 (NDC 55513-209-91). 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).

Storage

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

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

Information for Patients and Caregivers

This patient package insert provides information and instructions for people who will be receiving NEUPOGEN® and their caregivers. This patient package insert does not tell you everything about NEUPOGEN®. You should discuss any questions you have about treatment with NEUPOGEN® with your doctor.

What is NEUPOGEN®?

NEUPOGEN® is a man-made form of granulocyte colony-stimulating factor (G-CSF), which is made using the bacteria Escherichia coli. G-CSF is a substance naturally produced by the body. It stimulates the growth of neutrophils (nu-tro-fils), a type of white blood cell important in the body’s fight against infection. What is NEUPOGEN® used for?

NEUPOGEN® is used to treat neutropenia (nu-tro-peen-ee-ah), a condition where the body makes too few neutrophils. Neutropenia may be a long-standing condition where your body does not make enough neutrophils or it may be caused by drugs used to treat cancer. In some cases, your body may make enough neutrophils but as part of your treatment for cancer your doctor may want to increase the number of certain blood cells (CD34 cells) and collect them. The cells are collected using a process called apheresis (ay-fer-ree-sis). These collected cells are given back to you after you receive very high doses of treatment for cancer to make your blood counts get back to normal more quickly.

How does NEUPOGEN® work?

NEUPOGEN® works by helping your body make more neutrophils. To make sure NEUPOGEN® is working, your doctor will ask that you have regular blood tests to count the number of neutrophils you have. It is important that you follow your doctor’s instructions about getting these tests.

Who should not take NEUPOGEN®?

Do not take NEUPOGEN® if you are: Allergic to NEUPOGEN® (filgrastim) or any of its ingredients. See the end of this leaflet for a list of ingredients in NEUPOGEN®. Allergic to other medicines made using the bacteria E coli. Ask your doctor if you are not sure.

What important information do I need to know about taking NEUPOGEN®?

NEUPOGEN® may reduce your chance of getting an infection, but does not prevent all infections. An infection can still happen during the short time when your/your child's neutrophil levels are low. You must be alert and look for some of the common signs or symptoms of infection, such as fever, chills, rash, sore throat, diarrhea, redness, swelling, or pain around a cut or sore. If you/your child has any of these signs or symptoms during treatment with NEUPOGEN®, tell your doctor or nurse immediately. There is a possibility that you/your child could have a reaction at an injection site. If there is a lump, swelling, or bruising at an injection site that does not go away, call your doctor. If you have a sickle cell disorder, make sure that you tell your doctor before you start taking NEUPOGEN®. If you have a sickle cell crisis after getting NEUPOGEN®, tell your doctor right away. Talk to your doctor if you experience unusual bleeding or bruising while taking NEUPOGEN®, as this could mean a decrease of platelets which reduces the ability of blood to clot. Make sure your doctor knows about all medicines, and herbal or vitamin supplements you are taking before starting NEUPOGEN®. If you are taking lithium you may need more frequent blood tests. If you/your child are receiving NEUPOGEN® because you are also receiving chemotherapy, the last dose of NEUPOGEN® should be injected at least 24 hours before your next dose of chemotherapy. There is more information about NEUPOGEN® in the Physician Package Insert. If you have any questions, you should talk to your doctor.

What are possible serious side effects of NEUPOGEN®?

• Spleen Rupture. Your spleen may become enlarged and can rupture while taking NEUPOGEN®. A ruptured spleen can cause death. The spleen is located in the upper left section of your stomach area. Call your doctor right away if you/your child has pain in the left upper stomach area or left shoulder tip area. This pain could mean your/your child’s spleen is enlarged or ruptured.

• Serious Allergic Reactions. NEUPOGEN® can cause serious allergic reactions. These reactions can cause a rash over the whole body, shortness of breath, wheezing, dizziness, swelling around the mouth or eyes, fast pulse, and sweating. If you or your child starts to have any of these symptoms, stop using NEUPOGEN® and call your doctor or seek emergency care right away. If you/your child has an allergic reaction during the injection of NEUPOGEN®, stop the injection right away.

• A serious lung problem called acute respiratory distress syndrome (ARDS). Call your doctor or seek emergency care right away if you/your child has shortness of breath, trouble breathing or a fast rate of breathing.

What are the most common side effects of NEUPOGEN®?

The most common side effect you/your child may experience is aching in the bones and muscles. This aching can usually be relieved by taking a non-aspirin pain reliever such as acetaminophen. Some people experience redness, swelling, or itching at the site of injection. This may be an allergy to the ingredients in NEUPOGEN® or it may be a local reaction. If you are giving an injection to a child, look for signs of redness, swelling, or itching at the site of injection because they may not be able to tell you they are experiencing a reaction. If you notice any signs of a local reaction, call your doctor.

What about pregnancy or breastfeeding?

NEUPOGEN® has not been studied in pregnant women, and its effects on unborn babies are not known. If you take NEUPOGEN® while you are pregnant, it is possible that small amounts of it may get into your baby’s blood. It is not known if NEUPOGEN® can get into human breast milk. If you are pregnant, plan to become pregnant, think you may be pregnant, or are breast feeding, you should tell your doctor before using NEUPOGEN®. If you become pregnant during NEUPOGEN® treatment, you are encouraged to enroll in Amgen's Pregnancy Surveillance Program. You should call 1-800-77-AMGEN (1-800-772-6436) to enroll. If you breastfeed during NEUPOGEN® treatment, you are encouraged to enroll in Amgen’s Lactation Surveillance Program. You should call 1-800-77-AMGEN (1-800-772-6436) to enroll.

How to prepare and give a NEUPOGEN® injection?

NEUPOGEN® should be injected at the same time each day. If you miss a dose contact your doctor or nurse. You must always use the correct dose of NEUPOGEN®. Too little NEUPOGEN® may not protect you against infections, and too much NEUPOGEN® may cause too many neutrophils to be in your blood. Your doctor will determine your/your child’s correct dose based on your/your child's body weight. If you are giving someone else NEUPOGEN® injections, it is important that you know how to inject NEUPOGEN®, how much to inject, and how often to inject NEUPOGEN®. NEUPOGEN® is available as a liquid in vials or in prefilled syringes. When you receive your NEUPOGEN®, always check to see that:

• The name NEUPOGEN® appears on the package and vial or prefilled syringe label.

• The expiration date on the vial or prefilled syringe label has not passed. You should not use a vial or prefilled syringe after the date on the label.

• The strength of the NEUPOGEN® (number of micrograms in the colored dot on the package containing the vial or prefilled syringe) is the same as your doctor prescribed.

• The NEUPOGEN® liquid in the vial or in the prefilled syringe is clear and colorless. Do not use NEUPOGEN® if the contents of the vial or prefilled syringe appear discolored or cloudy, or if the vial or prefilled syringe appears to contain lumps, flakes, or particles.

If you are using vials of NEUPOGEN® only use the syringe that your doctor prescribes.

Your doctor or nurse will give you instructions on how to measure the correct dose of NEUPOGEN®. This dose will be measured in milliliters. You should only use a syringe that is marked in tenths of milliliters, or mL (for example, 0.2 mL). The doctor or nurse may refer to an mL as a cc (1 mL = 1 cc). If you do not use the correct syringe, you/your child could receive too much or too little NEUPOGEN®.

Only use disposable syringes and needles. Use the syringes only once and dispose of them as instructed by your doctor or nurse.

IMPORTANT: TO HELP AVOID POSSIBLE INFECTION, YOU SHOULD FOLLOW THESE INSTRUCTIONS.

Setting up for an injection

1. Find a clean flat working surface, such as a table. 2. Remove the vial or prefilled syringe of NEUPOGEN® from the refrigerator. Allow NEUPOGEN® to reach room temperature (this takes about 30 minutes). Vials or prefilled syringes should be used only once. DO NOT SHAKE 3. THE VIAL OR PREFILLED SYRINGE. Shaking may damage the NEUPOGEN®. If the vial or prefilled syringe has been shaken vigorously, the solution may appear foamy and it should not be used.

• Assemble the supplies you will need for an injection:

This image is provided by the National Library of Medicine.

Precautions with Alcohol

Alcohol-Filgrastim interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

NEUPOGEN

Look-Alike Drug Names

Neupogen - Neumega

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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