Filgrastim Injection

Before using filgrastim, tell your doctor or pharmacist if you are allergic to it; or to tbo-filgrastim/pegfilgrastim; or to other medications made in a similar manner (biotechnology-produced proteins using E. coli); or if you have any other allergies. This product may contain inactive ingredients (such as dry natural rubber/latex in the needle cover on the prefilled syringe), which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: sickle cell disease, heart disease, spleen problems, other blood disorders (e.g., myelodysplastic syndrome, congenital neutropenia), certain skin disorders (e.g., psoriasis).If you are scheduled to have radiation therapy, tell your doctor you are taking filgrastim. This medication should not be given during the time you are receiving radiation therapy.This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.

If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

Included as part of the PRECAUTIONS section.

NEUPOGEN®
(nu-po-jen)
(filgrastim) Injection

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 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.

Who should not take NEUPOGEN?

Do not take NEUPOGEN if you have had an allergic reaction to human G-CSFs such as NEUPOGEN (filgrastim) or Neulasta® (pegfilgrastim) or other forms of filgrastim.

What should I tell my doctor before taking NEUPOGEN?

Before you take NEUPOGEN, tell your doctor if you:

• have a sickle cell disorder.
• have a problem with your kidneys, as you may need more frequent urine tests.
• are allergic to latex. The needle cap on the prefilled syringes contains dry natural rubber (derived from latex). You should not give NEUPOGEN if you have latex allergies.
• are pregnant or plan to become pregnant. It is not known if NEUPOGEN will harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known if NEUPOGEN passes into your breast milk.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Why am I given NEUPOGEN if I was exposed to radiation?

Exposure to high levels of radiation damages bone marrow. Damage to the bone marrow can be deadly. NEUPOGEN increases your chance of survival.

Effectiveness of NEUPOGEN in increasing survival after radiation exposure was only studied in animals. NEUPOGEN given after deadly radiation levels could not be studied in people.

How will I receive NEUPOGEN?

• If you or your child is receiving NEUPOGEN because you or your child is also receiving chemotherapy, the last dose of NEUPOGEN should be injected at least 24 hours before your next dose of chemotherapy.
• If you or your child is receiving NEUPOGEN because you or your child has been exposed to harmful doses of radiation, your healthcare provider will monitor your response to NEUPOGEN. Your healthcare provider will advise you when to discontinue NEUPOGEN.

What are the possible serious side effects of NEUPOGEN?

NEUPOGEN may cause serious side effects, including:

• Spleen Rupture. Your spleen may become enlarged and can rupture while taking NEUPOGEN. A ruptured spleen can cause death. Call your doctor right away if you or your child has pain in the left upper stomach (abdomen) area or your left shoulder.
• A serious lung problem called acute respiratory distress syndrome (ARDS). Call your doctor or get emergency medical help right away if you or your child has shortness of breath with or without a fever, trouble breathing, or a fast rate of breathing.
• 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 get emergency help right away. If you or your child has an allergic reaction during the injection of NEUPOGEN, stop the injection right away.
• Sickle Cell Crises. You may have a serious sickle cell crisis if you have a sickle cell disorder and take NEUPOGEN. Serious and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving filgrastim. Call your doctor right away if you have symptoms of sickle cell crisis such as pain or difficulty breathing.
• Kidney injury (glomerulonephritis). Kidney injury has been seen in patients who received NEUPOGEN. Call your doctor right away if you experience puffiness in your face or ankles, blood in your urine or brown colored urine or you notice you urinate less than usual.
• Capillary leak syndrome. NEUPOGEN can cause fluid to leak from blood vessels into your body's tissues. This condition is called “Capillary Leak Syndrome” (CLS). CLS can quickly cause you to have symptoms that may become life-threatening. Get emergency medical help right away if you develop any of the following symptoms:
  • swelling or puffiness and are urinating less often
  • trouble breathing
  • swelling of your stomach-area (abdomen) and feeling of fullness
  • dizziness or feeling faint
  • a general feeling of tiredness
• Decreased platelet count (thrombocytopenia). Your doctor will check your blood during treatment with NEUPOGEN. Tell your doctor if you have unusual bleeding or bruising while taking NEUPOGEN. This could mean a decrease of platelets, which reduces the ability of blood to clot.
• Increased white blood cell count (leukocytosis). Your doctor will check your blood during treatment with NEUPOGEN.
• Inflammation of your blood vessels (cutaneous vasculitis). Tell your doctor if you develop purple spots or redness of your skin.

The most common side effects of NEUPOGEN include aching in the bones and muscles.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of NEUPOGEN. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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.

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 what 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

Note: The needle cap on the prefilled syringes contains dry natural rubber (derived from latex); persons with latex allergies should not administer these products.

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 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.

3. Assemble the supplies you will need for an injection:

• NEUPOGEN vial and disposable syringe and needle

• Or NEUPOGEN prefilled syringe with transparent (clear) plastic orange needle guard attached

• Two alcohol swabs and one cotton ball or gauze pad

• Puncture-proof disposal container

4. Wash your hands with soap and warm water.

HOW TO PREPARE THE DOSE OF NEUPOGEN IN VIALS OR PREFILLED SYRINGES

If you are using NEUPOGEN in a vial, follow the instructions in Section A. If you are using NEUPOGEN in a prefilled syringe, go to Section B.

Section A. Preparing the dose using NEUPOGEN in a vial

1. Take the cap off the vial. Clean the rubber stopper with one alcohol swab.

2. Check the package containing the syringe. If the package has been opened or damaged, do not use that syringe. Dispose of that syringe in the puncture-proof disposal container. If the syringe package is undamaged, open the package and remove the syringe.26

3. Pull the needle cap straight off the syringe. Then, pull back the plunger and draw air into the syringe. The amount of air drawn into the syringe should be the same amount (mL or cc) as the dose of NEUPOGEN that your doctor prescribed.

4. Keep the vial on the flat working surface and insert the needle straight down through the rubber stopper. Do not insert the needle through the rubber stopper more than once.

5. Push the plunger of the syringe down and inject the air from the syringe into the vial of NEUPOGEN.

6. Keeping the needle in the vial, turn the vial upside down. Make sure that the NEUPOGEN liquid is covering the tip of the needle.

7. Keeping the vial upside down, slowly pull back on the plunger to fill the syringe with NEUPOGEN liquid to the number (mL or cc) that matches the dose your doctor prescribed.

8. Keeping the needle in the vial, check for air bubbles in the syringe. If there are air bubbles, gently tap the syringe with your fingers until the air bubbles rise to the top of the syringe. Then slowly push the plunger up to force the air bubbles out of the syringe.

9. Keeping the tip of the needle in the liquid, once again pull the plunger back to the number on the syringe that matches your dose. Check again for air bubbles. The air in the syringe will not hurt you, but too large an air bubble can reduce your dose of NEUPOGEN. If there are still air bubbles, repeat the steps above to remove them.

10. Check again to make sure that you have the correct dose in the syringe. It is important that you use the exact dose prescribed by your doctor. Remove the syringe from the vial but do not lay it down or let the needle touch anything. (Go to “Selecting and preparing the injection site”).

Section B. Preparing the dose using NEUPOGEN in a prefilled syringe

1. Remove the syringe from the package and the tray. Check to see that the plastic orange needle guard is covering the barrel of the glass syringe. DO NOT push the orange needle guard over the needle cap before injection. This may activate or lock the needle guard. If the orange needle guard is covering the needle that means it has been activated. DO NOT use that syringe. Dispose of that syringe in the puncture-proof disposal container. Use a new syringe from the package.

2. Hold the syringe barrel through the needle guard windows with the needle pointing up. Holding the syringe with the needle pointing up helps to prevent medicine from leaking out of the needle. Carefully pull the needle cap straight off.

3. Check the syringe for air bubbles. If there are air bubbles, gently tap the syringe with your fingers until the air bubbles rise to the top of the syringe. Slowly push the plunger up to force the air bubbles out of the syringe.

4. Push the plunger up to the number (mL) on the syringe that matches the dose of NEUPOGEN that your doctor prescribed.

5. Check again to make sure the correct dose of NEUPOGEN is in the syringe.

6. Gently place the prefilled syringe with the window flat on your clean working surface so that the needle does not touch anything.

Selecting and preparing the injection site (for vials and prefilled syringes)

1. Choose an injection site. Four recommended injection sites for NEUPOGEN are:

• The outer area of your upper arms
• The abdomen, except for the two-inch area around your navel
• The front of your middle thighs
• The upper outer areas of your buttocks

Choose a new site each time you inject NEUPOGEN. Choosing a new site can help avoid soreness at any one site. Do not inject NEUPOGEN into an area that is tender, red, bruised, or hard or that has scars or stretch marks.

2. Clean the injection site with a new alcohol swab.

Injecting the dose of NEUPOGEN (for vials and prefilled syringes)

1. For injecting the dose of NEUPOGEN from a vial, remove the syringe and needle from the vial. For injecting the dose of NEUPOGEN from a prefilled syringe, pick up the prefilled syringe from the clean flat working surface by grabbing the sides of the needle guard with your thumb and forefinger.

2. Hold the syringe in the hand you will use to inject NEUPOGEN. Use the other hand to pinch a fold of skin at the cleaned injection site. Note: If using a prefilled syringe with a needle guard, hold the syringe barrel through the needle guard windows when giving the injection.

3. Holding the syringe like a pencil, use a quick “dart-like” motion to insert the needle either straight up and down (90 degree angle) or at a slight angle (45 degrees) into the skin.

4. Inject the prescribed dose subcutaneously as directed by your doctor, nurse, or pharmacist.

5. When the syringe is empty, pull the needle out of the skin and place a cotton ball or gauze over the injection site and press for several seconds.

6. Use the prefilled syringe with the needle guard or a syringe and vial only once. If you are using a syringe, DO NOT put the needle cap back on the needle. Discard the vial with any remaining NEUPOGEN liquid.

Activating the Needle Guard for the prefilled syringe after the injection has been given

1. After injecting NEUPOGEN from the prefilled syringe, do not recap the needle. Keep your hands behind the needle at all times. While holding the clear plastic finger grip of the syringe with one hand, grasp the orange needle guard with your free hand and slide the orange needle guard over the needle until the needle is completely covered and the needle guard clicks into place. NOTE: If an audible click is not heard, the needle guard may not be completely activated.

2. Place the prefilled syringe with the activated needle guard into a puncture-proof container for proper disposal as described below.

How should I dispose of used syringes, needles, and vials

• Put your used syringes, needles, and vials in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) loose needles, syringes and vials in your household trash.
• If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:
  • made of a heavy-duty plastic
  • can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out
  • upright and stable during use, leak-resistant, and
  • properly labeled to warn of hazardous waste inside the container.
• When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used syringes and needles. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal.33
• Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.

Always keep the sharps disposal container out of the reach of children.

How should I store NEUPOGEN?

• Store NEUPOGEN in the refrigerator between 36°F to 46°F (2°C to 8°C).
• Avoid freezing NEUPOGEN. If frozen, thaw in the refrigerator before giving a dose. Throw away (dispose of) NEUPOGEN if it has been frozen more than 1 time.
• Store NEUPOGEN in the carton to protect from light until you are ready to use it.
• Do not leave NEUPOGEN in direct sunlight.
• Avoid shaking NEUPOGEN.
• NEUPOGEN can be left out at room temperature for up to 24 hours. Throw away (dispose of) NEUPOGEN that has been left at room temperature for longer than 24 hours.

What are the ingredients in NEUPOGEN?

Active ingredient: filgrastim

Inactive ingredients: acetate, polysorbate 80, sodium, and sorbitol

Your pharmacist can provide more information about filgrastim.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 6.01. Revision date: 9/26/2012.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

• Splenic Rupture [see WARNINGS AND PRECAUTIONS]
• Acute Respiratory Distress Syndrome [see WARNINGS AND PRECAUTIONS]
• Serious Allergic Reactions [see WARNINGS AND PRECAUTIONS]
• Sickle Cell Disorders [see WARNINGS AND PRECAUTIONS]
• Glomerulonephritis [See WARNINGS AND PRECAUTIONS]
• Alveolar Hemorrhage and Hemoptysis [see WARNINGS AND PRECAUTIONS]
• Capillary Leak Syndrome [see WARNINGS AND PRECAUTIONS]
• Thrombocytopenia [see WARNINGS AND PRECAUTIONS]
• Leukocytosis [see WARNINGS AND PRECAUTIONS]
• Cutaneous Vasculitis [see WARNINGS AND PRECAUTIONS]

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 with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Adverse Reactions in Patients with Cancer Receiving Myelosuppressive Chemotherapy

The following adverse reaction data in Table 2 are from three randomized, placebo-controlled studies in patients with:

• small cell lung cancer receiving standard dose chemotherapy with cyclophosphamide, doxorubicin, and etoposide (Study 1)
• small cell lung cancer receiving ifosfamide, doxorubicin, and etoposide (Study 2), and
• non-Hodgkin's lymphoma (NHL) receiving doxorubicin, cyclophosphamide, vindesine, bleomycin, methylprednisolone, and methotrexate (“ACVBP”) or mitoxantrone, ifosfamide, mitoguazone, teniposide, methotrexate, folinic acid, methylprednisolone, and methotrexate (“VIM3”) (Study 3).

A total of 451 patients were randomized to receive subcutaneous NEUPOGEN 230 mcg/m² (Study 1), 240 mcg/m² (Study 2) or 4 or 5 mcg/kg/day (Study 3) (n = 294) or placebo (n = 157). The patients in these studies were median age 61 (range 29 to 78) years and 64% were male. The ethnicity was 95% Caucasian, 4% African American, and 1% Asian.

Table 2: Adverse Reactions in Patients with Cancer Receiving Myelosuppressive Chemotherapy (With ≥ 5% Higher Incidence in NEUPOGEN Compared to Placebo)

System Organ Class Preferred Term	NEUPOGEN (N = 294)	Placebo (N = 157)
Blood and lymphatic system disorders
Thrombocytopenia	38%	29%
Gastrointestinal disorders
Nausea	43%	32%
General disorders and administration site conditions
Pyrexia	48%	29%
Chest pain	13%	6%
Pain	12%	6%
Fatigue	20%	10%
Musculoskeletal and connective tissue disorders
Back pain	15%	8%
Arthralgia	9%	2%
Bone pain	11%	6%
Pain in extremity*	7%	3%
Nervous system disorders
Dizziness	14%	3%
Respiratory, thoracic and mediastinal disorders
Cough	14%	8%
Dyspnea	13%	8%
Skin and subcutaneous tissue disorders
Rash	14%	5%
Investigations
Blood lactate dehydrogenase increased	6%	1%
Blood alkaline phosphatase increased	6%	1%
*Percent difference (NEUPOGEN - Placebo) was 4%.

Adverse events with ≥ 5% higher incidence in NEUPOGEN patients compared to placebo and associated with the sequelae of the underlying malignancy or cytotoxic chemotherapy delivered included anemia, constipation, diarrhea, oral pain, vomiting, asthenia, malaise, edema peripheral, hemoglobin decreased, decreased appetite, oropharyngeal pain, and alopecia.

Adverse Reactions in Patients with Acute Myeloid Leukemia

Adverse reaction data below are from a randomized, double-blind, placebo-controlled study in patients with AML (Study 4) who received an induction chemotherapy regimen of intravenous daunorubicin days 1, 2, and 3; cytosine arabinoside days 1 to 7; and etoposide days 1 to 5 and up to 3 additional courses of therapy (induction 2, and consolidation 1, 2) of intravenous daunorubicin, cytosine arabinoside, and etoposide. The safety population included 518 patients randomized to receive either 5 mcg/kg/day NEUPOGEN (n = 257) or placebo (n = 261). The median age was 54 (range 16 to 89) years and 54% were male.

Adverse reactions with ≥ 2% higher incidence in NEUPOGEN patients compared to placebo included epistaxis, back pain, pain in extremity, erythema, and rash maculo-papular.

Adverse events with ≥ 2% higher incidence in NEUPOGEN patients compared to placebo and associated with the sequelae of the underlying malignancy or cytotoxic chemotherapy included diarrhea, constipation, and transfusion reaction.

Adverse Reactions in Patients with Cancer Undergoing Bone Marrow Transplantation

The following adverse reaction data are from one randomized, no treatment-controlled study in patients with acute lymphoblastic leukemia or lymphoblastic lymphoma receiving high-dose chemotherapy (cyclophosphamide or cytarabine, and melphalan) and total body irradiation (Study 5) and one randomized, no treatment controlled study in patients with Hodgkin's disease (HD) and NHL undergoing high-dose chemotherapy and autologous bone marrow transplantation (Study 6). Patients receiving autologous bone marrow transplantation only were included in the analysis. A total of 100 patients received either 30 mcg/kg/day as a 4 hour infusion (Study 5) or 10 mcg/kg/day or 30 mcg/kg/day as a 24 hour infusion (Study 6) NEUPOGEN (n = 72), no treatment control or placebo (n = 28). The median age was 30 (range 15 to 57) years, 57% were male.

Adverse reactions with ≥ 5% higher incidence in NEUPOGEN patients compared to patients receiving no NEUPOGEN included rash and hypersensitivity.

Adverse reactions in patients receiving intensive chemotherapy followed by autologous BMT with ≥ 5% higher incidence in NEUPOGEN patients compared to patients receiving no NEUPOGEN included thrombocytopenia, anemia, hypertension, sepsis, bronchitis, and insomnia.

Adverse Reactions in Patients with Cancer Undergoing Autologous Peripheral Blood Progenitor Cell Collection

The adverse reaction data in Table 3 are from a series of 7 trials in patients with cancer undergoing mobilization of autologous peripheral blood progenitor cells for collection by leukapheresis. Patients (n = 166) in all these trials underwent a similar mobilization/collection regimen: NEUPOGEN was administered for 6 to 8 days, in most cases the apheresis procedure occurred on days 5, 6, and 7. The dosage of NEUPOGEN ranged between 5 to 30 mcg/kg/day and was administered subcutaneously by injection or continuous infusion. The median age was 39 (range 15 to 67) years, and 48% were male.

Table 3: Adverse Reactions in Patients with Cancer Undergoing Autologous PBPC in the Mobilization Phase ( ≥ 5% Incidence in NEUPOGEN Patients)

System Organ Class Preferred Term	Mobilization Phase (N = 166)
Musculoskeletal and connective tissue disorders
Bone pain	30%
General disorders and administration site conditions
Pyrexia	16%
Investigations
Blood alkaline phosphatase increased	11%
Nervous system disorders
Headache	10%

Adverse Reactions in Patients with Severe Chronic Neutropenia

The following adverse reaction data were identified in a randomized, controlled study in patients with SCN receiving NEUPOGEN (Study 7). 123 patients were randomized to a 4 month observation period followed by subcutaneous NEUPOGEN treatment or immediate subcutaneous NEUPOGEN treatment. The median age was 12 years (range 7 months to 76 years) and 46% were male. The dosage of NEUPOGEN was determined by the category of neutropenia. Initial dosage of NEUPOGEN:

• Idiopathic neutropenia: 3.6 mcg/kg/day
• Cyclic neutropenia: 6 mcg/kg/day
• Congenital neutropenia: 6 mcg/kg/day divided 2 times per day

The dosage was increased incrementally to 12 mcg/kg/day divided 2 times per day if there was no response.

Adverse reactions with ≥ 5% higher incidence in NEUPOGEN patients compared to patients receiving no NEUPOGEN included arthralgia, bone pain, back pain, muscle spasms, musculoskeletal pain, pain in extremity, splenomegaly, anemia, upper respiratory tract infection, and urinary tract infection (upper respiratory tract infection and urinary tract infection were higher in the NEUPOGEN arm, total infection related events were lower in NEUPOGEN treated patients), epistaxis, chest pain, diarrhea, hypoesthesia, and alopecia.

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 using NEUPOGEN, the incidence of antibodies binding to filgrastim 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 filgrastim 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.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use 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 AND PRECAUTIONS]
• acute respiratory distress syndrome [see WARNINGS AND PRECAUTIONS]
• anaphylaxis [see WARNINGS AND PRECAUTIONS]
• sickle cell disorders [see WARNINGS AND PRECAUTIONS]
• glomerulonephritis [see WARNINGS AND PRECAUTIONS]
• alveolar hemorrhage and hemoptysis [see WARNINGS AND PRECAUTIONS]
• capillary leak syndrome [see WARNINGS AND PRECAUTIONS]
• leukocytosis [see WARNINGS AND PRECAUTIONS]
• cutaneous vasculitis [see WARNINGS AND PRECAUTIONS]
• Sweet's syndrome (acute febrile neutrophilic dermatosis)
• decreased bone density and osteoporosis in pediatric patients receiving chronic treatment with NEUPOGEN

Read the entire FDA prescribing information for Neupogen (Filgrastim Injection)

Read More »

• If you have an allergy to filgrastim or any other part of filgrastim injection.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into the fatty part of the skin.
• It may be given as a shot into a vein.
• To gain the most benefit, do not miss doses.
• Keep taking filgrastim injection as you have been told by your doctor or other health care provider, even if you feel well.
• If you will be giving yourself the shot, your doctor or nurse will teach you how to give the shot.
• Follow how to use as you have been told by the doctor or read the package insert.
• Before using this medicine, take it out of the refrigerator and leave it at room temperature for 30 minutes.
• Do not use if the solution is cloudy, leaking, or has particles.
• Do not use if solution changes color.
• Do not shake the solution.
• Wash your hands before and after you give the shot.
• Do not give into skin that is irritated, bruised, red, infected, or scarred.
• Move the site where you give the shot with each shot.
• Throw away any part left over after the dose is given.
• Throw syringe away after use. Do not use the same syringe more than one time.
• Throw away needles in a needle/sharp disposal box. Do not reuse needles or other items. When the box is full, follow all local rules for getting rid of it. Talk with a doctor or pharmacist if you have any questions.
• Do not switch between different brands of filgrastim injection without first talking with the doctor.
• Do not switch between different forms of this medicine without first talking with the doctor.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Dark urine.
• A fast heartbeat.
• Dizziness or passing out.
• Sweating a lot.
• Shortness of breath.
• Fast breathing.
• Fever.
• Coughing up blood.
• Feeling very tired or weak.
• Any unexplained bruising or bleeding.
• Purple spots or redness of the skin.
• Very bad headache.
• Swelling.
• Enlarged and ruptured spleens have happened with filgrastim injection. Sometimes, ruptured spleens have been deadly. Call your doctor right away if you have left upper stomach pain or left shoulder pain.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Back pain.
• Bone pain.
• Joint pain.
• Cough.
• Headache.
• Upset stomach.
• Feeling tired or weak.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.