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  • Neupogen 30 MU vials & 30 MU, 48 MU Pre-filled Syringe
    / Amgen


    Active Ingredient
    Filgrastim 30 MU/ml (0.3 mg/ml), 30 MU/0.5 ml (0.6 mg/ml), 48 MU/0.5 ml (0.96 mg/ml)

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Vial

    5 X 30 MU/ml

    partial basket chart 25519 14229

    Pre-filled Syringe (solution for injection)

    30 IU / 0.5 ml

    partial basket chart 3757 14243

    Pre-filled Syringe (solution for injection)

    48 IU / 0.5 ml (0.96 mg/ml)

    partial basket chart 3758 14244

    Related information


    Dosage

    Myelosuppressive chemotherapy: The recommended dose of Neupogen is 0.5 MU (5 µg)/kg/day. The first dose of Neupogen should be administered at least 24 hours after cytotoxic chemotherapy. In randomized clinical trials, a subcutaneous dose of 230 µg/m²/day (4.0 to 8.4 µg/kg/day) was used.
    Daily dosing with Neupogen should continue until the expected neutrophil nadir is passed and the neutrophil count has recovered to the normal range. Following established chemotherapy for solid tumors, lymphomas, and lymphoid leukemia, it is expected that the duration of treatment required to fulfill these criteria will be up to 14 days. Following induction and consolidation treatment for acute myeloid leukemia the duration of treatment may be substantially longer (up to 38 days) depending on the type, dose and schedule of cytotoxic
    chemotherapy used.
    In patients receiving cytotoxic chemotherapy, a transient increase in neutrophil counts is typically seen 1 to 2 days after initiation of Neupogen therapy. However, for a sustained therapeutic response, Neupogen therapy should not be discontinued before the expected nadir has passed and the neutrophil count has recovered to the normal range. Premature discontinuation of Neupogen therapy, prior to the time of the expected neutrophil nadir, is not recommended.
    Method of administration: Neupogen may be given as a daily subcutaneous injection or as a daily intravenous infusion diluted in 5% glucose solution given over 30 minutes. The subcutaneous route is preferred in most cases.
    There is some evidence from a study of single dose administration that intravenous dosing may shorten the duration of effect. The clinical relevance of this finding to multiple dose administration is not clear. The choice of route should depend on the individual clinical circumstance.
    In patients treated with high-dose cytotoxic chemotherapy followed by bone marrow transplantation: The recommended starting dose of Neupogen is 1.0 MU (10 µg)/kg/day. The first dose of Neupogen should be administered at least 24 hours after cytotoxic chemotherapy and at least 24 hours after bone marrow infusion. Once the neutrophil nadir has been passed, the daily dose of Neupogen should be titrated against the neutrophil response as follows:
    Neutrophil Count> 1.0 x 10^9/l for 3 consecutive days: Reduce to 0.5 MU (5 µg)/kg/day.
    Then, if ANC* remains > 1.0 x 10^9 /l for 3 more consecutive days: Discontinue Neupogen.
    If the ANC* decreases to < 1.0 x 10^9/l during the treatment period the dose of Neupogen should be re-escalated according to the above steps.
    *ANC = absolute neutrophil count
    Method of administration: Neupogen may be given as a 30 minute or 24 hour intravenous infusion or 1.0 MU (10 µg)/kg/day given by continuous 24 hour subcutaneous infusion. Neupogen should be diluted in 20 ml of 5% glucose solution.
    For the mobilization of PBPCs in patients undergoing myelosuppressive or myeloablative therapy followed by autologous PBPC transplantation: The recommended dose of Neupogen for PBPC mobilization when used alone is 1.0 MU (10 µg)/kg/day for 5 to 7 consecutive days. Timing of leukapheresis: one or two leukapheresis on days 5 and 6 are often sufficient. In other circumstances, additional leukapheresis may be necessary. Neupogen dosing should be maintained until the last leukapheresis.
    The recommended dose of Neupogen for PBPC mobilization after myelosuppressive chemotherapy is 0.5 MU (5 µg)/kg/day from the first day after completion of chemotherapy until the expected neutrophil nadir is passed and the neutrophil count has recovered to the normal range. Leukapheresis should be performed during the period when the ANC rises from < 0.5 x 10^9/l to > 5.0 x 10^9/l. For patients who have not had extensive chemotherapy, one leukapheresis is often sufficient. In other circumstances, additional leukapheresis are recommended.
    Method of administration: Neupogen for PBPC mobilization when used alone:
    Neupogen may be given as a 24 hour subcutaneous continuous infusion or subcutaneous injection. For infusions Neupogen should be diluted in 20 ml of 5% glucose solution.
    Neupogen for PBPC mobilization after myelosuppressive chemotherapy:
    Neupogen should be given by subcutaneous injection.
    For the mobilization of PBPCs in normal donors prior to allogeneic PBPC transplantation: For PBPC mobilization in normal donors, Neupogen should be administered at 1.0 MU (10 µg)/kg/day for 4 to 5 consecutive days. Leukapheresis should be started at day 5 and continued until day 6 if needed in order to collect 4 x 10^6 CD34+cells/kg recipient body weight.
    Method of administration: Neupogen should be given by subcutaneous injection.
    In patients with severe chronic neutropenia (SCN): Congenital neutropenia: the recommended starting dose is 1.2 MU (12 µg)/kg/day, as a single dose or in
    divided doses.
    Idiopathic or cyclic neutropenia: the recommended starting dose is 0.5 MU (5 µg)/kg/day, as a single dose or in divided doses.
    Dose adjustment: Neupogen should be administered daily by subcutaneous injection until the neutrophil count has reached and can be maintained at more than 1.5 x 10^9/l. When the response has been obtained the minimal effective dose to maintain this level should be established. Long-term daily administration is required to maintain an adequate neutrophil count. After one to two weeks of therapy, the initial dose may be doubled or halved depending upon the patient’s response. Subsequently the dose may be individually adjusted every 1 to 2 weeks to maintain the average neutrophil count between 1.5 x 10^9/l and 10 x 10^9/l. A faster schedule of dose escalation may be considered in patients presenting with severe infections. In clinical trials, 97% of patients who responded had a complete response at doses ≤ 24 µg/kg/day. The long-term safety of Neupogen administration above 24 µg/kg/day in patients with SCN has not been established.
    Method of administration: Congenital, idiopathic or cyclic neutropenia: Neupogen should be given by subcutaneous injection.
    Older people: Clinical trials with Neupogen have included a small number of elderly patients but special studies have not been performed in this group and therefore specific dosage recommendations cannot be made.
    Patients with renal impairment: Studies of Neupogen in patients with severe impairment of renal or hepatic function demonstrate that it exhibits a similar pharmacokinetic and pharmacodynamic profile to that seen in normal individuals. Dose adjustment is not required in these circumstances.
    Pediatric use in the SCN and cancer settings: Sixty-five percent of the patients studied in the SCN trial program were under 18 years of age. The efficacy of treatment was clear for this age group, which included most patients with congenital neutropenia. There were no differences in the safety profiles for pediatric patients treated for SCN.
    Data from clinical studies in pediatric patients indicate that the safety and efficacy of Neupogen are similar in both adults and children receiving cytotoxic chemotherapy.
    The dosage recommendations in pediatric patients are the same as those in adults receiving myelosuppressive cytotoxic chemotherapy.


    Indications

    – Reduction in the duration and severity of neutropenia in patients treated with highly myelosuppressive chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes).
    – Reduction in the duration of neutropenia in patients undergoing high-dose cytotoxic chemotherapy followed by bone marrow transplantation.
    – In children or adults with severe congenital neutropenia, cyclic neutropenia or idiopathic neutropenia, a history of clinically important infections within the last 12 months and three documented episodes of neutropenia (with an ANC < 5 x 1000000000), long-term administration of Neupogen is indicated to increase neutrophil counts and to reduce infections.
    – Neupogen is indicated for the mobilization of autologous peripheral blood progenitor cells alone or following myelosuppressive chemotherapy and the mobilization of peripheral blood progenitor cells in normal donors (allogeneic PBPC).


    Contra-Indications

    Hypersensitivity to the active substance or to any of the excipients.


    Special Precautions

    Special warning and precautions across indications
    Hypersensitivity: Hypersensitivity, including anaphylactic reactions, occurring on initial or subsequent treatment have been reported in patients treated with Neupogen. Permanently discontinue Neupogen in patients with clinically significant hypersensitivity. Do not administer Neupogen to patients with a history of hypersensitivity to filgrastim or pegfilgrastim.
    Pulmonary adverse effects: Pulmonary adverse effects, in particular interstitial lung disease, have been reported after G-CSF administration. Patients with a recent history of lung infiltrates or pneumonia may be at higher risk. The onset of pulmonary signs, such as cough, fever and dyspnea in association with radiological signs of pulmonary infiltrates and deterioration in pulmonary function may be preliminary signs of acute respiratory distress syndrome (ARDS). Neupogen should be discontinued and appropriate treatment given.
    Glomerulonephritis: Glomerulonephritis has been reported in patients receiving filgrastim and pegfilgrastim. Generally, events of glomerulonephritis resolved after dose reduction or withdrawal of filgrastim and pegfilgrastim. Urinalysis monitoring is recommended.
    Special warnings and precautions associated with co-morbidities
    Sickle cell trait and sickle cell disease: Sickle cell crises, in some cases fatal, have been reported with the use of Neupogen in patients with sickle cell trait or sickle cell disease. Physicians should use caution when prescribing Neupogen in patients with sickle cell trait or sickle cell disease.
    Osteoporosis: Monitoring of bone density may be indicated in patients with underlying osteoporotic bone diseases who undergo continuous therapy with Neupogen for more than 6 months.
    Special precautions in cancer patients
    Neupogen should not be used to increase the dose of cytotoxic chemotherapy beyond established dosage regimens.
    Risks associated with increased doses of chemotherapy: Special caution should be used when treating patients with high-dose chemotherapy, because improved tumor outcome has not been demonstrated and intensified doses of chemotherapeutic agents may lead to increased toxicities including cardiac, pulmonary, neurologic, and dermatologic effects (please refer to the prescribing information of the specific chemotherapy agents used).
    Effect of chemotherapy on erythrocytes and thrombocytes: Treatment with Neupogen alone does not preclude thrombocytopenia and anemia due to myelosuppressive chemotherapy. Because of the potential of receiving higher doses of chemotherapy (e.g. full doses on the prescribed schedule) the patient may be at greater risk of thrombocytopenia and anemia. Regular monitoring of platelet count and hematocrit is recommended. Special care should be taken when administering single or combination chemotherapeutic agents which are known to cause severe thrombocytopenia.
    The use of Neupogen mobilized PBPCs has been shown to reduce the depth and duration of thrombocytopenia following myelosuppressive or myeloablative chemotherapy.
    Other special precautions: The effects of Neupogen in patients with substantially reduced myeloid progenitors have not been studied.
    Neupogen acts primarily on neutrophil precursors to exert its effect in elevating neutrophil counts. Therefore in patients with reduced precursors neutrophil response may be diminished (such as those treated with extensive radiotherapy or chemotherapy, or those with bone marrow infiltration by tumor).
    Vascular disorders, including veno-occlusive disease and fluid volume disturbances, have been reported occasionally in patients undergoing high-dose chemotherapy followed by transplantation.
    There have been reports of GvHD and fatalities in patients receiving G-CSF after allogeneic bone marrow transplantation.
    Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient abnormal bone scans. This should be considered when interpreting bone-imaging results.
    Special precautions in patients undergoing PBPC mobilization
    Mobilization: There are no prospectively randomized comparisons of the two recommended mobilization methods (Neupogen alone, or in combination with myelosuppressive chemotherapy) within the same patient population. The degree of variation between individual patients and between laboratory assays of CD34+cells mean that direct comparison between different studies is difficult. It is therefore difficult to recommend an optimum method. The choice of mobilization method should be considered in relation to the overall objectives of treatment for an individual patient.
    Prior exposure to cytotoxic agents: Patients who have undergone very extensive prior myelosuppressive therapy may not show sufficient mobilization of PBPC to achieve the recommended minimum yield (≥ 2.0 x 10^6 CD34+ cells/kg) or acceleration of platelet recovery, to the same degree.
    Special precautions in SCN patients
    Neupogen should not be administered to patients with severe congenital neutropenia who develop leukemia or have evidence of leukemic evolution.
    Other special precautions
    Causes of transient neutropenia, such as viral infections should be excluded.
    Hematuria was common and proteinuria occurred in a small number of patients. Regular urinalysis should be performed to monitor these events.
    The safety and efficacy in neonates and patients with autoimmune neutropenia have not been established.
    See prescribing information for full details.


    Side Effects

    The most serious adverse reactions that may occur during Neupogen treatment include: anaphylactic reaction, serious pulmonary adverse events (including interstitial pneumonia and ARDS), capillary leak syndrome, severe splenomegaly/splenic rupture, transformation to myelodysplastic syndrome or leukemia in SCN patients, GvHD in patients receiving allogeneic bone marrow transfer or peripheral blood cell progenitor cell transplant and sickle cell crisis in patients with sickle cell disease.
    The most commonly reported adverse reactions are pyrexia, musculoskeletal pain (which includes bone pain, back pain, arthralgia, myalgia, pain in extremity, musculoskeletal pain, musculoskeletal chest pain, neck pain), anemia, vomiting, and nausea. In clinical trials in cancer patients musculoskeletal pain was mild or moderate in 10%, and severe in 3% of patients.
    See prescribing information for full details.


    Drug interactions

    The safety and efficacy of Neupogen given on the same day as myelosuppressive cytotoxic chemotherapy have not been definitively established. In view of the sensitivity of rapidly dividing myeloid cells to myelosuppressive cytotoxic chemotherapy, the use of Neupogen is not recommended in the period from 24 hours before to 24 hours after chemotherapy. Preliminary evidence from a small number of patients treated concomitantly with Neupogen and 5-Fluorouracil indicates that the severity of neutropenia may be exacerbated.
    Possible interactions with other hematopoietic growth factors and cytokines have not yet been investigated in clinical trials.
    Since lithium promotes the release of neutrophils, lithium is likely to potentiate the effect of Neupogen.
    Although this interaction has not been formally investigated, there is no evidence that such an interaction is harmful.


    Pregnancy and Lactation

    Pregnancy: There are no or limited amount of data from the use of filgrastim in pregnant women. Neupogen is not recommended during pregnancy.
    Breast-feeding: It is unknown whether filgrastim/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Neupogen therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
    See prescribing information for full details.


    Overdose

    The effects of Neupogen overdosage have not been established. Discontinuation of Neupogen therapy usually results in a 50% decrease in circulating neutrophils within 1 to 2 days, with a return to normal levels in 1 to 7 days.


    Important notes

    Incompatibilities: Neupogen should not be diluted with saline solutions.
    Diluted filgrastim may be adsorbed to glass and plastic materials. 
    Storage: 
    Store at 2°C to 8°C.
    Shelf life: 30 months.
    See prescribing information for full details.


    Manufacturer
    Amgen Europe B.V., Breda, Netherlands.
    Licence holder
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