(filgrastim-aafi)

Prescribing Information
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5 WARNINGS AND PRECAUTIONS

5 WARNINGS AND PRECAUTIONS

5.1 Splenic Rupture

Splenic rupture, including fatal cases, has been reported following the administration of filgrastim products. Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture.

5.2 Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) has been reported in patients receiving filgrastim products. Evaluate patients who develop fever and lung infiltrates or respiratory distress for ARDS. Discontinue NIVESTYM in patients with ARDS.

5.3 Serious Allergic Reactions

Serious allergic reactions, including anaphylaxis, have been reported in patients receiving filgrastim products. The majority of reported events occurred upon initial exposure. Provide symptomatic treatment for allergic reactions. Allergic reactions, including anaphylaxis, in patients receiving filgrastim products can recur within days after the discontinuation of initial anti-allergic treatment. Permanently discontinue NIVESTYM in patients with serious allergic reactions. NIVESTYM is contraindicated in patients with a history of serious allergic reactions to human granulocyte colony-stimulating factors such as filgrastim products or pegfilgrastim products.

5.4 Sickle Cell Disorders

Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving filgrastim products. Discontinue NIVESTYM if sickle cell crisis occurs.

5.5 Glomerulonephritis

Glomerulonephritis has occurred in patients receiving filgrastim products. The diagnoses were based upon azotemia, hematuria (microscopic and macroscopic), proteinuria, and renal biopsy. Generally, events of glomerulonephritis resolved after dose reduction or discontinuation of filgrastim products. If glomerulonephritis is suspected, evaluate for cause. If causality is likely, consider dose-reduction or interruption of NIVESTYM.

5.6 Alveolar Hemorrhage and Hemoptysis

Alveolar hemorrhage manifesting as pulmonary infiltrates and hemoptysis requiring hospitalization have been reported in healthy donors treated with filgrastim products undergoing peripheral blood progenitor cell (PBPC) collection mobilization. Hemoptysis resolved with discontinuation of filgrastim products. The use of NIVESTYM for PBPC mobilization in healthy donors is not an approved indication.

5.7 Capillary Leak Syndrome

Capillary leak syndrome (CLS) has been reported after G-CSF administration, including filgrastim products, and is characterized by hypotension, hypoalbuminemia, edema and hemoconcentration. Episodes vary in frequency, severity and may be life-threatening if treatment is delayed. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care.

5.8 Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)

Patients with Severe Chronic Neutropenia

Confirm the diagnosis of SCN before initiating NIVESTYM therapy.

MDS and AML have been reported to occur in the natural history of congenital neutropenia without cytokine therapy. Cytogenetic abnormalities, transformation to MDS, and AML have also been observed in patients treated with filgrastim products 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 filgrastim products on the development of abnormal cytogenetics and the effect of continued filgrastim products administration in patients with abnormal cytogenetics or MDS are unknown. Monitor patients for signs and symptoms of MDS/AML in these settings. If a patient with SCN develops abnormal cytogenetics or myelodysplasia‚ the risks and benefits of continuing NIVESTYM should be carefully considered.

Patients with Breast and Lung Cancer

MDS and AML have been associated with the use of filgrastim products in conjunction with chemotherapy and/or radiotherapy in patients with breast and lung cancer. Monitor patients for signs and symptoms of MDS/AML in these settings.

5.9 Thrombocytopenia

Thrombocytopenia has been reported in patients receiving filgrastim products. Monitor platelet counts.

5.10 Leukocytosis

Patients with Cancer Receiving Myelosuppressive Chemotherapy

White blood cell counts of 100‚000/mm3 or greater were observed in approximately 2% of patients receiving filgrastim at dosages above 5 mcg/kg/day. In patients with cancer receiving NIVESTYM as an adjunct to myelosuppressive chemotherapy‚ to avoid the potential risks of excessive leukocytosis‚ it is recommended that NIVESTYM therapy be discontinued if the ANC surpasses 10‚000/mm3 after the chemotherapy-induced ANC nadir has occurred. Monitor CBCs at least twice weekly during therapy. Dosages of NIVESTYM that increase the ANC beyond 10‚000/mm3 may not result in any additional clinical benefit. In patients with cancer receiving myelosuppressive chemotherapy‚ discontinuation of filgrastim therapy usually resulted in a 50% decrease in circulating neutrophils within 1 to 2 days‚ with a return to pretreatment levels in 1 to 7 days.

Peripheral Blood Progenitor Cell Collection and Therapy

During the period of administration of NIVESTYM for PBPC mobilization in patients with cancer, discontinue NIVESTYM if the leukocyte count rises to > 100,000/mm3.

5.11 Cutaneous Vasculitis

Cutaneous vasculitis has been reported in patients treated with filgrastim products. In most cases‚ the severity of cutaneous vasculitis was moderate or severe. Most of the reports involved patients with SCN receiving long-term filgrastim therapy. Hold NIVESTYM therapy in patients with cutaneous vasculitis. NIVESTYM may be started at a reduced dose when the symptoms resolve and the ANC has decreased.

5.12 Potential Effect on Malignant Cells

NIVESTYM is a growth factor that primarily stimulates neutrophils. The granulocyte colony-stimulating factor (G-CSF) receptor through which NIVESTYM acts has also been found on tumor cell lines. The possibility that NIVESTYM acts as a growth factor for any tumor type cannot be excluded. The safety of filgrastim products in chronic myeloid leukemia (CML) and myelodysplasia has not been established.

When NIVESTYM 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.

5.13 Simultaneous Use with Chemotherapy and Radiation Therapy Not Recommended

The safety and efficacy of NIVESTYM 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 NIVESTYM in the period 24 hours before through 24 hours after the administration of cytotoxic chemotherapy [see Dosage and Administration (2.2)].

The safety and efficacy of NIVESTYM have not been evaluated in patients receiving concurrent radiation therapy. Avoid the simultaneous use of NIVESTYM with chemotherapy and radiation therapy.

5.14 Nuclear Imaging

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.

5.15 Aortitis

Aortitis has been reported in patients receiving Filgrastim products. It may occur as early as the first week after start of therapy. Manifestations may include generalized signs and symptoms such as fever, abdominal pain, malaise, back pain, and increased inflammatory markers (e.g., c-reactive protein and white blood cell count). Consider aortitis in patients who develop these signs and symptoms without known etiology. Discontinue NIVESTYM if aortitis is suspected.

Medication Guide

MEDICATION GUIDE

Patient Information
NIVESTYM (Neye-ves-tim)
(filgrastim-aafi)
injection

What is NIVESTYM?

NIVESTYM is a man-made form of granulocyte colony-stimulating factor (G-CSF). G-CSF is a substance produced by the body. It stimulates the growth of neutrophils, a type of white blood cell important in the body's fight against infection.

Do not take NIVESTYM if you have had a serious allergic reaction to human G-CSFs such as filgrastim products or pegfilgrastim products.

Before you take NIVESTYM, tell your healthcare provider about all of your medical conditions, including if you:

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have a sickle cell disorder.
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have kidney problems.
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are receiving radiation therapy.
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are pregnant or plan to become pregnant. It is not known if NIVESTYM will harm your unborn baby.
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are breastfeeding or plan to breastfeed. It is not known if NIVESTYM passes into your breast milk.

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

How will I receive NIVESTYM?

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NIVESTYM injections can be given by a healthcare provider by intravenous (IV) infusion or under your skin (subcutaneous injection). Your healthcare provider may decide subcutaneous injections can be given at home by you or your caregiver. If NIVESTYM is given at home, see the detailed "Instructions for Use" that comes with your NIVESTYM for information on how to prepare and inject a dose of NIVESTYM.
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You and your caregiver should be shown how to prepare and inject NIVESTYM before you use it, by your healthcare provider.
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You should not try to inject a dose of NIVESTYM less than 0.3 mL (180 mcg) from a NIVESTYM prefilled syringe. A dose less than 0.3 mL cannot be accurately measured using the NIVESTYM prefilled syringe.
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Your healthcare provider will tell you how much NIVESTYM to inject and when to inject it. Do not change your dose or stop NIVESTYM unless your healthcare provider tells you to.
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If you are receiving NIVESTYM because you are also receiving chemotherapy, your dose of NIVESTYM should be injected at least 24 hours before or 24 hours after your dose of chemotherapy. Your healthcare provider will do blood tests to monitor your white blood cell count, and if necessary, adjust your NIVESTYM dose.
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If you miss a dose of NIVESTYM, talk to your healthcare provider about when you should give your next dose.

What are the possible side effects of NIVESTYM?

NIVESTYM may cause serious side effects, including:

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Spleen rupture. Your spleen may become enlarged and can rupture. A ruptured spleen can cause death. Call your healthcare provider right away if you have pain in the left upper stomach (abdomen) area or your left shoulder.
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A serious lung problem called acute respiratory distress syndrome (ARDS). Call your healthcare provider or get emergency medical help right away if you have shortness of breath with or without a fever, trouble breathing, or a fast rate of breathing.
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Serious allergic reactions. NIVESTYM can cause serious allergic reactions. These reactions can cause a rash over your whole body, shortness of breath, wheezing, dizziness, swelling around your mouth or eyes, fast heart rate, and sweating. If you have any of these symptoms, stop using NIVESTYM and call your healthcare provider or get emergency medical help right away.
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Sickle cell crises. You may have a serious sickle cell crisis, which could lead to death, if you have a sickle cell disorder and receive NIVESTYM. Call your healthcare provider right away if you have symptoms of sickle cell crisis such as pain or difficulty breathing.
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Kidney injury (glomerulonephritis). NIVESTYM can cause kidney injury. Call your healthcare provider right away if you develop any of the following symptoms:
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swelling of your face or ankles
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blood in your urine or dark colored urine
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you urinate less than usual
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Capillary leak syndrome. NIVESTYM 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:
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swelling or puffiness and are urinating less than usual
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trouble breathing
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swelling of your stomach area (abdomen) and feeling of fullness
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dizziness or feeling faint
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a general feeling of tiredness
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Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML).
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NIVESTYM may increase the risk of developing a precancerous condition called MDS or a type of blood cancer called AML in people who were born with low white blood cell counts (congenital neutropenia).
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If you have breast cancer or lung cancer, when NIVESTYM is used with chemotherapy and radiation therapy, or with radiation therapy only, you may have an increased risk of developing MDS or AML.
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Symptoms of MDS and AML may include tiredness, fever, and easy bruising or bleeding.
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Call your healthcare provider if you develop any of these symptoms during treatment with NIVESTYM.
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Decreased platelet count (thrombocytopenia). Your healthcare provider will check your blood during treatment with NIVESTYM. Tell your healthcare provider if you have unusual bleeding or bruising during treatment with NIVESTYM. This could be a sign of decreased platelet counts, which may reduce the ability of your blood to clot.
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Increased white blood cell count (leukocytosis). Your healthcare provider will check your blood during treatment with NIVESTYM.
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Inflammation of your blood vessels (cutaneous vasculitis). Tell your healthcare provider right away if you develop purple spots or redness of your skin.
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Inflammation of the aorta (aortitis). Inflammation of the aorta (the large blood vessel which transports blood from the heart to the body) has been reported in patients who received NIVESTYM. Symptoms may include fever, abdominal pain, feeling tired, and back pain. Call your healthcare provider if you experience these symptoms.

The most common side effects experienced in patients receiving NIVESTYM include:

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Patients with cancer receiving chemotherapy: fever, pain, rash, cough, and shortness of breath
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Patients with acute myeloid leukemia receiving chemotherapy: pain, nose bleed, and rash
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Patients with cancer receiving chemotherapy followed by bone marrow transplant: rash
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Patients who are having their own blood cells collected: bone pain, fever, and headache
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Patients with severe chronic neutropenia: pain, decreased red blood cells, nose bleed, diarrhea, reduced sensation, and hair loss

These are not all the possible side effects of NIVESTYM. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store NIVESTYM?

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Store NIVESTYM in the refrigerator between 36°F to 46°F (2°C to 8°C).
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Do not freeze.
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Keep NIVESTYM in the original carton to protect from light or physical damage. Do not leave NIVESTYM in direct sunlight.
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Do not shake NIVESTYM.
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Take NIVESTYM out of the refrigerator 30 minutes before use and allow it to reach room temperature before preparing an injection.
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Throw away (dispose of) any NIVESTYM that has been left at room temperature for longer than 24 hours.
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After you inject your dose, throw away (dispose of) any unused NIVESTYM left in the vials or prefilled syringes. Do not save unused NIVESTYM in the vials or prefilled syringes for later use.

Keep NIVESTYM out of the reach of children.

General information about the safe and effective use of NIVESTYM.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use NIVESTYM for a condition for which it was not prescribed. Do not give NIVESTYM to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about NIVESTYM that is written for healthcare professionals.

What are the ingredients in NIVESTYM?

Active ingredient: (filgrastim-aafi)

Inactive ingredients: acetate, polysorbate 80, sodium, sorbitol, and water for Injection

Manufactured by Hospira, Inc., a Pfizer Company, Lake Forest, IL 60045 USA
US License No. 1974

Distributed by Pfizer Labs, division of Pfizer Inc., New York, NY 10001 USA

LAB-0935-5.0
For more information go to www.pfizer.com or call 1-800-438-1985.

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This Patient Information has been approved by the U.S. Food and Drug Administration     Revised: March 2023

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