Important Safety Information and Indications
NEUPOGEN® is contraindicated in patients with a history of serious allergic reactions to human granulocyte colony‐stimulating factors, such as filgrastim or pegfilgrastim.
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
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
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.
Sickle Cell Disorders
Sickle cell crisis, in some cases fatal, has been reported with the use of NEUPOGEN® in patients with sickle cell trait, or sickle cell disease.
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 causality is likely, consider dose-reduction or interruption of NEUPOGEN®.
Alveolar Hemorrhage and Hemoptysis
Alveolar hemorrhage, manifesting as pulmonary infiltrates and hemoptysis requiring hospitalization, has been reported in NEUPOGEN®‐treated healthy donors undergoing peripheral blood progenitor cell (PBPC) collection mobilization. Hemoptysis resolved with discontinuation of NEUPOGEN®. The use of NEUPOGEN® for PBPC mobilization in healthy donors is not an approved indication.
Capillary Leak Syndrome
Capillary leak syndrome (CLS) has been reported after G‐CSF administration, including NEUPOGEN®, 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 the need for intensive care.
Patients with Severe Chronic Neutropenia (SCN):
Confirm the diagnosis of SCN before initiating NEUPOGEN® therapy.
Myelodysplastic syndrome (MDS) and acute myelogenous leukemia (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. 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.
Thrombocytopenia has been reported in patients receiving NEUPOGEN®. Monitor platelet counts.
Patients with Cancer Receiving Myelosuppressive Chemotherapy:
White blood cell counts ≥ 100,000/mm3 were observed in about 2% of patients who received NEUPOGEN® at dosages > 5 mcg/kg/day. It is recommended that NEUPOGEN® therapy be discontinued if the absolute neutrophil count (ANC) surpasses 10,000/mm3 after the chemotherapy-induced ANC nadir has occurred. Monitor CBCs at least twice weekly during therapy. Dosages of NEUPOGEN® that increase the ANC beyond 10,000/mm3 may not result in any additional clinical benefit. Discontinuation of NEUPOGEN® 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 (PBPC) Collection and Therapy:
During the period of administration of NEUPOGEN® for PBPC mobilization in patients with cancer,
discontinue NEUPOGEN® if the leukocyte count rises to > 100,000/mm3.
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. Hold NEUPOGEN® therapy in patients with cutaneous vasculitis. NEUPOGEN® may be restarted at a reduced dose when the symptoms resolve and the ANC has decreased.
Potential Effect on Malignant Cells
The granulocyte colony-stimulating factor (G-CSF) receptor through which filgrastim acts has also been found on tumor cell lines. The possibility that NEUPOGEN® acts as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, cannot be excluded. The safety of filgrastim 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 on reinfusion of tumor cells has not been well studied, and the limited data available are inconclusive.
Simultaneous Use with Chemotherapy and Radiation Not Recommended
The safety and efficacy of NEUPOGEN® given simultaneously with cytotoxic chemotherapy have not been established. Do not use NEUPOGEN® in the period of 24 hours before or after the administration of cytotoxic chemotherapy. The safety and efficacy of NEUPOGEN® have not been evaluated in patients receiving concurrent radiation therapy. Avoid the simultaneous use of NEUPOGEN® with chemotherapy and radiation therapy.
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.
The most common adverse reactions in patients:
- with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs (≥ 5% difference in incidence compared to placebo) are anemia, constipation, diarrhea, oral pain, vomiting, asthenia, malaise, peripheral edema, decreased hemoglobin, decreased appetite, oropharyngeal pain, and alopecia.
- with AML (≥ 2% difference in incidence) are epistaxis, back pain, pain in extremity, erythema, maculopapular rash, diarrhea, constipation, and transfusion reaction.
- with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by BMT (≥ 5% difference in incidence) are rash, hypersensitivity, thrombocytopenia, anemia, hypertension, sepsis, bronchitis, and insomnia.
- undergoing peripheral blood progenitor cell mobilization and collection (≥ 5% incidence) are bone pain, pyrexia, increased blood alkaline phosphatase, and headache.
- with severe chronic neutropenia (≥ 5% difference in incidence) are arthralgia, bone pain, back pain, muscle spasms, musculoskeletal pain, pain in extremity, splenomegaly, anemia, upper respiratory tract infection, urinary tract infection, epistaxis, chest pain, diarrhea, hypoesthesia, and alopecia.
Please see the full Prescribing Information for NEUPOGEN.
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.
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).
Patients with Cancer Undergoing Bone Marrow Transplantation
NEUPOGEN® is indicated to reduce the duration of neutropenia and neutropenia-related clinical sequelae‚ eg, febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation.
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.
Patients with Severe Chronic Neutropenia
NEUPOGEN® is indicated for chronic administration to reduce the incidence and duration of sequelae of severe neutropenia (eg‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia.