Neupogen

NEUPOGEN is a leukocyte growth factor indicated to

• Decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever (
  1.1 Patients with Cancer Receiving Myelosuppressive Chemotherapy

  NEUPOGEN is indicated to decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a significant incidence of severe neutropenia with fever

  [see Clinical Studies (14.1)]

  .
  )
• Reduce the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML) (
  1.2 Patients with Acute Myeloid Leukemia Receiving Induction or Consolidation Chemotherapy

  NEUPOGEN is indicated for reducing the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML)

  [see Clinical Studies (14.2)]

  .
  )
• Reduce the duration of neutropenia and neutropenia-related clinical sequelae‚ e.g.‚ febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation (BMT) (
  1.3 Patients with Cancer Undergoing Bone Marrow Transplantation

  NEUPOGEN is indicated to reduce the duration of neutropenia and neutropenia-related clinical sequelae‚ e.g.‚ febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation

  [see Clinical Studies (14.3)]

  .
  )
• Mobilize autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis (
  1.4 Patients Undergoing Autologous Peripheral Blood Progenitor Cell Collection and Therapy

  NEUPOGEN is indicated for the mobilization of autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis

  [see Clinical Studies (14.4)]

  .
  )
• Reduce the incidence and duration of sequelae of severe neutropenia (e.g.‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia (
  1.5 Patients with Severe Chronic Neutropenia

  NEUPOGEN is indicated for chronic administration to reduce the incidence and duration of sequelae of neutropenia (e.g.‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia

  [see Clinical Studies (14.5)]

  .
  )
• Increase survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome) (
  1.6 Patients Acutely Exposed to Myelosuppressive Doses of Radiation (Hematopoietic Syndrome of Acute Radiation Syndrome)

  NEUPOGEN is indicated to increase survival in patients acutely exposed to myelosuppressive doses of radiation

  [see Clinical Studies (14.6)]

  .
  )

• Patients with cancer receiving myelosuppressive chemotherapy or induction and/or consolidation chemotherapy for AML
  • Recommended starting dose is 5 mcg/kg/day subcutaneous injection, short intravenous infusion (15 to 30 minutes), or continuous intravenous infusion. See Full Prescribing Information for recommended dosage adjustments and timing of administration (
    2.1 Dosage in Patients with Cancer Receiving Myelosuppressive Chemotherapy or Induction and/or Consolidation Chemotherapy for AML

    The recommended starting dosage of NEUPOGEN is 5 mcg/kg/day‚ administered as a single daily injection by subcutaneous injection‚ by short intravenous infusion (15 to 30 minutes)‚ or by continuous intravenous infusion. Obtain a complete blood count (CBC) and platelet count before instituting NEUPOGEN therapy and monitor twice weekly during therapy. Consider dose escalation in increments of 5 mcg/kg for each chemotherapy cycle‚ according to the duration and severity of the absolute neutrophil count (ANC) nadir. Recommend stopping NEUPOGEN if the ANC increases beyond 10‚000/mm³

    [see Warnings and Precautions (5.10)]

    .

    Administer NEUPOGEN at least 24 hours after cytotoxic chemotherapy. Do not administer NEUPOGEN within the 24-hour period prior to chemotherapy

    [see Warnings and Precautions (5.13)]

    . A transient increase in neutrophil count is typically seen 1 to 2 days after initiation of NEUPOGEN therapy.

    Therefore, to ensure a sustained therapeutic response‚ administer NEUPOGEN daily for up to 2 weeks or until the ANC has reached 10‚000/mm³following 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.
    )
• Patients with cancer undergoing bone marrow transplantation
  • 10 mcg/kg/day given as an intravenous infusion no longer than 24 hours. See Full Prescribing Information for recommended dosage adjustments and timing of administration (
    2.2 Dosage in Patients with Cancer Undergoing Bone Marrow Transplantation

    The recommended dosage of NEUPOGEN following bone marrow transplantation (BMT) is 10 mcg/kg/day given as an intravenous infusion no longer than 24 hours. Administer the first dose of NEUPOGEN at least 24 hours after cytotoxic chemotherapy and at least 24 hours after bone marrow infusion. Monitor CBCs and platelet counts frequently following marrow transplantation.

    During the period of neutrophil recovery‚ titrate the daily dosage of NEUPOGEN against the neutrophil response

    (see Table 1)

    .

    Table 1. Recommended Dosage Adjustments During Neutrophil Recovery in Patients with Cancer Following BMT

    Absolute Neutrophil Count	NEUPOGEN Dosage Adjustment
    When ANC greater than 1,000/mm3for 3 consecutive days	Reduce to 5 mcg/kg/dayIf ANC decreases to less than 1,000/mm3at any time during the 5 mcg/kg/day administration‚ increase NEUPOGEN to 10 mcg/kg/day‚ and then follow the above steps.
    Then, if ANC remains greater than 1,000/mm3for 3 more consecutive days	Discontinue NEUPOGEN
    Then, if ANC decreases to less than 1,000/mm3	Resume at 5 mcg/kg/day
    )
• Patients undergoing autologous peripheral blood progenitor cell collection and therapy
  • 10 mcg/kg/day subcutaneous injection (
    2.3 Dosage in Patients Undergoing Autologous Peripheral Blood Progenitor Cell Collection and Therapy

    The recommended dosage of NEUPOGEN for the mobilization of autologous peripheral blood progenitor cells (PBPC) is 10 mcg/kg/day given by subcutaneous injection. Administer NEUPOGEN for at least 4 days before the first leukapheresis procedure and continue until the last leukapheresis. Although the optimal duration of NEUPOGEN administration and leukapheresis schedule have not been established‚ administration of NEUPOGEN for 6 to 7 days with leukaphereses on days 5‚ 6‚ and 7 was found to be safe and effective

    [see Clinical Studies (14.4)]

    . Monitor neutrophil counts after 4 days of NEUPOGEN‚ and discontinue NEUPOGEN if the white blood cell (WBC) count rises to greater than 100‚000/mm³.
    )
  • Administer for at least 4 days before first leukapheresis procedure and continue until last leukapheresis (
    2.3 Dosage in Patients Undergoing Autologous Peripheral Blood Progenitor Cell Collection and Therapy

    The recommended dosage of NEUPOGEN for the mobilization of autologous peripheral blood progenitor cells (PBPC) is 10 mcg/kg/day given by subcutaneous injection. Administer NEUPOGEN for at least 4 days before the first leukapheresis procedure and continue until the last leukapheresis. Although the optimal duration of NEUPOGEN administration and leukapheresis schedule have not been established‚ administration of NEUPOGEN for 6 to 7 days with leukaphereses on days 5‚ 6‚ and 7 was found to be safe and effective

    [see Clinical Studies (14.4)]

    . Monitor neutrophil counts after 4 days of NEUPOGEN‚ and discontinue NEUPOGEN if the white blood cell (WBC) count rises to greater than 100‚000/mm³.
    )
• Patients with congenital neutropenia
  • Recommended starting dose is 6 mcg/kg subcutaneous injection twice daily (
    2.4 Dosage in Patients with Severe Chronic Neutropenia

    Prior to starting NEUPOGEN in patients with suspected chronic neutropenia, confirm the diagnosis of severe chronic neutropenia (SCN) by evaluating serial CBCs with differential and platelet counts‚ and evaluating bone marrow morphology and karyotype. The use of NEUPOGEN prior to confirmation of a correct diagnosis of SCN may impair diagnostic efforts and may thus impair or delay evaluation and treatment of an underlying condition‚ other than SCN‚ causing the neutropenia.

    The recommended starting dosage in patients with Congenital Neutropenia is 6 mcg/kg as a twice daily subcutaneous injection and the recommended starting dosage in patients with Idiopathic or Cyclic Neutropenia is 5 mcg/kg as a single daily subcutaneous injection.

    Dosage Adjustments in Patients with Severe Chronic Neutropenia

    Chronic daily administration is required to maintain clinical benefit. Individualize the dosage 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 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 greater than or equal to 100 mcg/kg/day.

    Monitor CBCs for Dosage Adjustments

    During the initial 4 weeks of NEUPOGEN therapy and during the 2 weeks following any dosage adjustment‚ monitor CBCs with differential and platelet counts. Once a patient is clinically stable‚ monitor CBCs with differential and platelet counts monthly during the first year of treatment. Thereafter, if the patient is clinically stable, less frequent routine monitoring is recommended.
    )
• Patients with cyclic or idiopathic neutropenia
  • Recommended starting dose is 5 mcg/kg subcutaneous injection daily (
    2.4 Dosage in Patients with Severe Chronic Neutropenia

    Prior to starting NEUPOGEN in patients with suspected chronic neutropenia, confirm the diagnosis of severe chronic neutropenia (SCN) by evaluating serial CBCs with differential and platelet counts‚ and evaluating bone marrow morphology and karyotype. The use of NEUPOGEN prior to confirmation of a correct diagnosis of SCN may impair diagnostic efforts and may thus impair or delay evaluation and treatment of an underlying condition‚ other than SCN‚ causing the neutropenia.

    The recommended starting dosage in patients with Congenital Neutropenia is 6 mcg/kg as a twice daily subcutaneous injection and the recommended starting dosage in patients with Idiopathic or Cyclic Neutropenia is 5 mcg/kg as a single daily subcutaneous injection.

    Dosage Adjustments in Patients with Severe Chronic Neutropenia

    Chronic daily administration is required to maintain clinical benefit. Individualize the dosage 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 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 greater than or equal to 100 mcg/kg/day.

    Monitor CBCs for Dosage Adjustments

    During the initial 4 weeks of NEUPOGEN therapy and during the 2 weeks following any dosage adjustment‚ monitor CBCs with differential and platelet counts. Once a patient is clinically stable‚ monitor CBCs with differential and platelet counts monthly during the first year of treatment. Thereafter, if the patient is clinically stable, less frequent routine monitoring is recommended.
    )
• Patients acutely exposed to myelosuppressive doses of radiation
  • 10 mcg/kg/day subcutaneous injection (
    2.5 Dosage in Patients Acutely Exposed to Myelosuppressive Doses of Radiation (Hematopoietic Syndrome of Acute Radiation Syndrome)

    The recommended dose of NEUPOGEN is 10 mcg/kg as a single daily subcutaneous injection for patients exposed to myelosuppressive doses of radiation. Administer NEUPOGEN as soon as possible after suspected or confirmed exposure to radiation doses greater than 2 gray (Gy).

    Estimate a patient's absorbed radiation dose (i.e., level of radiation exposure) based on information from public health authorities, biodosimetry if available, or clinical findings such as time to onset of vomiting or lymphocyte depletion kinetics.

    Obtain a baseline CBC and then serial CBCs approximately every third day until the ANC remains greater than 1,000/mm³for 3 consecutive CBCs. Do not delay administration of NEUPOGEN if a CBC is not readily available.

    Continue administration of NEUPOGEN until the ANC remains greater than 1,000/mm³for 3 consecutive CBCs or exceeds 10,000/mm³after a radiation-induced nadir.
    )

NEUPOGEN is a clear, colorless, preservative-free solution available as:

Available data from published studies, including several observational studies of pregnancy outcomes in women exposed to filgrastim products and those who were unexposed, have not established an association with NEUPOGEN use during pregnancy and major birth defects, miscarriage, or adverse maternal or fetal outcomes

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

• Fatal splenic rupture: Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture. (
  5.1 Splenic Rupture

  Splenic rupture, including fatal cases, has been reported following the administration of NEUPOGEN. Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture.
  )
• Acute respiratory distress syndrome (ARDS): Evaluate patients who develop fever and lung infiltrates or respiratory distress for ARDS. Discontinue NEUPOGEN in patients with ARDS. (
  5.2 Acute Respiratory Distress Syndrome

  Acute respiratory distress syndrome (ARDS) has been reported in patients receiving NEUPOGEN. Evaluate patients who develop fever and lung infiltrates or respiratory distress for ARDS. Discontinue NEUPOGEN in patients with ARDS.
  )
• Serious allergic reactions, including anaphylaxis: Permanently discontinue NEUPOGEN in patients with serious allergic reactions. (
  5.3 Serious Allergic Reactions

  Serious allergic reactions, including anaphylaxis, have been reported in patients receiving NEUPOGEN. The majority of reported events occurred upon initial exposure. Provide symptomatic treatment for allergic reactions. Allergic reactions, including anaphylaxis, in patients receiving NEUPOGEN can recur within days after the discontinuation of initial anti-allergic treatment. Permanently discontinue NEUPOGEN in patients with serious allergic reactions. NEUPOGEN is contraindicated in patients with a history of serious allergic reactions to human granulocyte colony-stimulating factors such as filgrastim or pegfilgrastim.
  )
• Fatal sickle cell crises: Discontinue NEUPOGEN if sickle cell crisis occurs. (
  5.4 Sickle Cell Disorders

  Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving filgrastim products. Discontinue NEUPOGEN if sickle cell crisis occurs.
  )
• Glomerulonephritis: Evaluate and consider dose-reduction or interruption of NEUPOGEN if causality is likely. (
  5.5 Glomerulonephritis

  Glomerulonephritis has occurred in patients receiving NEUPOGEN. 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 NEUPOGEN. If glomerulonephritis is suspected, evaluate for cause. If causality is likely, consider dose-reduction or interruption of NEUPOGEN.
  )
• Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML): Monitor patients with breast and lung cancer using NEUPOGEN in conjunction with chemotherapy and/or radiotherapy for signs and symptoms of MDS/AML. (
  5.8 Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)

  Patients with Severe Chronic Neutropenia

  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. 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. 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 NEUPOGEN should be carefully considered.

  Patients with Breast and Lung Cancer

  MDS and AML have been associated with the use of NEUPOGEN 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.
  )
• Thrombocytopenia: Monitor platelet counts. (
  5.9 Thrombocytopenia

  Thrombocytopenia has been reported in patients receiving NEUPOGEN. Monitor platelet counts.
  )
• Aortitis: Aortitis has been reported in patients receiving NEUPOGEN. Discontinue NEUPOGEN if aortitis is suspected. (
  5.15 Aortitis

  Aortitis has been reported in patients receiving NEUPOGEN. 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 NEUPOGEN if aortitis is suspected.
  )