"Nov. 29, 2012 (Chicago) -- For cancer patients undergoing chemotherapy who have found their complaints of general mental fogginess and haziness dismissed by their doctors as not being a real medical condition, vindication has arrived.
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. NEUPOGEN is contraindicated in patients with a history of serious allergic reactions to human granulocyte colony-stimulating factors such as filgrastim or pegfilgrastim.
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 glomerulonephritis is suspected, evaluate for cause. 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 have 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 a need for intensive care.
Patients With Severe Chronic Neutropenia
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. 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.
Thrombocytopenia has been reported in patients receiving NEUPOGEN. Monitor platelet counts.
Patients with Cancer Receiving Myelosuppressive Chemotherapy
White blood cell counts of 100‚000/mm³ or greater were observed in approximately 2% of patients receiving NEUPOGEN at dosages above 5 mcg/kg/day. In patients with cancer receiving NEUPOGEN as an adjunct to myelosuppressive chemotherapy‚ to avoid the potential risks of excessive leukocytosis‚ it is recommended that NEUPOGEN 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 NEUPOGEN 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 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 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 started at a reduced dose when the symptoms resolve and the ANC has decreased.
Potential Effect On Malignant Cells
NEUPOGEN is a growth factor that primarily stimulates neutrophils. The granulocyte-colony-stimulating factor (G-CSF) receptor through which filgrastim acts has also been found on tumor cell lines. The possibility that filgrastim acts as a growth factor for any tumor type 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 of reinfusion of tumor cells has not been well studied‚ and the limited data available are inconclusive.
Simultaneous Use With Chemotherapy And Radiation Therapy Not Recommended
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].
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.
Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION).
Advise patients of the following risks and potential risks with NEUPOGEN:
- Rupture or enlargement of the spleen may occur. Symptoms include left upper quadrant abdominal pain or left shoulder pain. Advise patients to report pain in these areas to their physician immediately [see WARNINGS AND PRECAUTIONS].
- Dyspnea, with or without fever, progressing to Acute Respiratory Distress Syndrome, may occur. Advise patients to report dyspnea to their physician immediately [see WARNINGS AND PRECAUTIONS].
- Serious allergic reactions may occur, which may be signaled by rash‚ facial edema‚ wheezing‚ dyspnea‚ hypotension‚ or tachycardia. Advise patients to seek immediate medical attention if signs or symptoms of hypersensitivity reaction occur [see WARNINGS AND PRECAUTIONS].
- In patients with sickle cell disease, sickle cell crisis and death have occurred. Discuss potential risks and benefits for patients with sickle cell disease prior to the administration of human granulocyte colony-stimulating factors [see WARNINGS AND PRECAUTIONS].
- Glomerulonephritis may occur. Symptoms include swelling of the face or ankles, dark colored urine or blood in the urine, or a decrease in urine production. Advise patients to report signs or symptoms of glomerulonephritis to their physician immediately [see WARNINGS AND PRECAUTIONS].
- Cutaneous vasculitis may occur, which may be signaled by purpura or erythema. Advise patients to report signs or symptoms of vasculitis to their physician immediately [see WARNINGS AND PRECAUTIONS].
- Advise females of reproductive potential that NEUPOGEN should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus [see Use In Specific Populations].
- Advise patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome) that efficacy studies of NEUPOGEN for this indication could not be conducted in humans for ethical and feasibility reasons and that, therefore, approval of this use was based on efficacy studies conducted in animals [see Clinical Studies].
Carcinogenesis, Mutagenesis, Impairment Of Fertility
The carcinogenic potential of filgrastim has not been studied. Filgrastim failed to induce bacterial gene mutations in either the presence or absence of a drug metabolizing enzyme system. Filgrastim had no observed effect on the fertility of male or female rats at doses up to 500 mcg/kg.
Use In Specific Populations
Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women. The potential risk to the fetus is unknown. Reports in the scientific literature have described transplacental passage of NEUPOGEN in pregnant women when administered ≤ 30 hours prior to preterm delivery ( ≤ 30 weeks gestation). NEUPOGEN should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Effects of filgrastim on prenatal development have been studied in rats and rabbits. No malformations were observed in either species. Filgrastim has been shown to have adverse effects in pregnant rabbits at doses 2 to 10 times higher than the human doses. In pregnant rabbits showing signs of maternal toxicity, reduced embryo-fetal survival (at 20 and 80 mcg/kg/day) and increased abortions (at 80 mcg/kg/day) were observed. In pregnant rats, no maternal or fetal effects were observed at doses up to 575 mcg/kg/day.
Offspring of rats administered filgrastim during the peri-natal and lactation periods exhibited a delay in external differentiation and growth retardation ( ≥ 20 mcg/kg/day) and slightly reduced survival rate (100 mcg/kg/day).
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 women who are breastfeeding.
In patients with cancer receiving myelosuppressive chemotherapy‚ 15 pediatric patients median age 2.6 (range 1.2 to 9.4) years with neuroblastoma were treated with myelosuppressive chemotherapy (cyclophosphamide‚ cisplatin‚ doxorubicin‚ and etoposide) followed by subcutaneous NEUPOGEN at doses of 5, 10, or 15 mcg/kg/day for 10 days (n = 5/dose) (Study 8). The pharmacokinetics of NEUPOGEN in pediatric patients after chemotherapy are similar to those in adults receiving the same weight-normalized doses, suggesting no age-related differences in the pharmacokinetics of NEUPOGEN. In this population‚ NEUPOGEN was well tolerated. There was one report of palpable splenomegaly and one report of hepatosplenomegaly 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.
The safety and effectiveness of NEUPOGEN have been established in pediatric patients with SCN [see Clinical Studies]. In a phase 3 study (Study 7) to assess the safety and efficacy of NEUPOGEN in the treatment of SCN, 123 patients with a median age of 12 years (range 7 months to 76 years) were studied. Of the 123 patients, 12 were infants (7 months to 2 years of age), 49 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 731 patients in the surveillance study, 429 were pediatric patients < 18 years of age (range 0.9 to 17) [see INDICATIONS AND USAGE, DOSAGE AND ADMINISTRATION, and Clinical Studies].
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.
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 PRECAUTIONS and ADVERSE REACTIONS].
The use of NEUPOGEN to increase survival in pediatric patients acutely exposed to myelosuppressive doses of radiation is based on studies conducted in animals and clinical data supporting the use of NEUPOGEN in other approved indications [see DOSAGE AND ADMINISTRATION and Clinical Studies].
Among 855 subjects enrolled in 3 randomized, placebo-controlled trials of NEUPOGEN-treated patients receiving 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.
Clinical studies of NEUPOGEN in other approved indications (i.e., 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.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 8/14/2015
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