Neupogen 0.5 ml Injection

NEUPOGEN u00ae is indicated for the reduction in the duration of neutropenia and the incidence of febrile neutropenia in patients treated with established cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemia and myelodysplastic syndromes) and for the reduction in the duration of neutropenia and its clinical sequelae in patients undergoing myeloablative therapy, followed by bone marrow transplantation.

In patients, children or adults, with severe congenital, cyclic, or idiopathic neutropenia with an Absolute Neutrophil Count (ANC) u2264 0,5x109/l, long term administration of NEUPOGEN is indicated to increase neutrophil count and to reduce the incidence and duration of infections.

The mobilisation of autologous peripheral blood progenitor cells alone, or following myelosuppressive chemotherapy, in order to accelerate haematopoietic recovery by infusion of such cells after myelosuppressive or myeloablative therapy. The mobilisation of peripheral blood progenitor cells in normal donors (allogeneic) PBPC.

NEUPOGEN is indicated in patients with advanced HIV infection and neutropenia (absolute neutrophil count (ANC) < 1 x 109/l) to allow scheduled dosing of anti-retroviral medication.

Therapy should only be given in collaboration with an oncology centre which has experience in G-CSF treatment and haematology and has the necessary diagnostic facilities. The mobilisation and apheresis procedures should be performed in collaboration with an oncology-haematology centre with acceptable experience in this field and where the monitoring of haematopoietic progenitor cells can be correctly performed.

The recommended dose of NEUPOGEN is 0,5 MU (5 u03bcg)/kg/day. The first dose of NEUPOGEN should not be administered within 24 hours of cytotoxic chemotherapy or bone marrow infusion. NEUPOGEN may be given as a daily subcutaneous injection or as a daily intravenous infusion diluted in 5 % glucose solution, given over 30 minutes (refer to instructions on dilution). The subcutaneous route is preferred in most cases.

Daily dosing with NEUPOGEN should continue until the expected nadir is passed and the neutrophil count has recovered to the normal range. Following established chemotherapy for solid tumours, 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 leukaemia (AML), 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 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.

The recommended starting dose of NEUPOGEN, following BMT, is 1,0 MU (10 u03bcg)/kg/day, given as an IV infusion of 4 or 24 hours, or as a continuous 24-hour subcutaneous infusion. NEUPOGEN should be diluted in 20 ml of 5 % glucose solution. For patients receiving BMT, the first dose of NEUPOGEN should be administered at least 24 hours after cytotoxic chemotherapy, but within 24 hours of bone marrow infusion.

The efficacy and safety of NEUPOGEN given for longer than 28 days in this setting have not been established.

NEUPOGEN should not be administered to patients with known sensitivity to the product or its constituents. NEUPOGEN should not be used to increase the dose of cytotoxic chemotherapy beyond established dosage regimens. NEUPOGEN should not be administered to patients with severe congenital neutropenia (Kostmannu2019s syndrome) with abnormal cytogenetics. Studies have not been performed with NEUPOGEN in patients with severe impairment of renal or hepatic function and therefore its use in this patient group cannot be recommended.

Hypersensitivity, pulmonary toxicity, sickle cell crises. (See SIDE EFFECTS AND SPECIAL PRECAUTIONS). Sickle cell crises, in some cases fatal, have been reported with the use of NEUPOGEN in subjects with sickle cell disease. Medical practitioners should exercise caution when considering the use of NEUPOGEN in patients with sickle cell disease, and only after careful evaluation of the potential risks and benefits.

The safety and efficacy of NEUPOGEN given on the same day as myelosuppressive cytotoxic chemotherapy has not been 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. 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 haematopoietic 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. This interaction has not been formally investigated.

Increased haematopoietic 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 safety of NEUPOGEN in pregnant or lactating women has not been established. There are reports in the literature that transplacental passage of filgrastim in pregnant women has been demonstrated. Studies in animals have shown reproductive toxicity. In pregnancy, the possible risk of NEUPOGEN use to the foetus must be weighed against the expected therapeutic benefit. NEUPOGEN should not be used in pregnancy. It is not known whether NEUPOGEN is excreted in human milk. Women on NEUPOGEN should not breastfeed their babies.

Not provided in the text.

Administration of NEUPOGEN at the recommended dosage is frequently associated with musculoskeletal pain, specifically in medullar bones, that was mild to moderate in 10 %, and severe in 3 % of patients. Less frequent adverse events include urinary abnormalities (predominantly mild or moderate dysuria). NEUPOGEN did not increase the incidence of clinical adverse events associated with cytotoxic chemotherapy. Adverse events reported included nausea and vomiting, alopecia, diarrhoea, neutropenic fever, mucositis, fever, fatigue, anorexia, dyspnoea, headache, cough, skin rash, chest pain, generalised weakness, sore throat, stomatitis, constipation and unspecified pain.

Reversible, dose-dependent and usually mild or moderate elevations of lactate dehydrogenase (LDH), alkaline phosphatase, serum uric acid and gamma-glutamyl transpeptidase occurred with NEUPOGEN in approximately 50 %, 35 %, 25 % and 10 % of patients, respectively, at recommended doses. Transient decreases in blood pressure have been reported. Vascular disorders, including veno-occlusive disease and fluid volume disturbances, have been reported in patients undergoing high dose chemotherapy followed by autologous bone marrow transplantation. The causal association with NEUPOGEN has not been established.

Symptoms suggestive of allergic-type have been reported in rare cases; approximately half of these were associated with the initial dose. Overall, reports were more common after IV administration. In some cases, re-challenge resulted in a recurrence of symptoms. Rare events (less than 1 in 7 000) of cutaneous vasculitis have been reported in patients treated with NEUPOGEN. The mechanism of vasculitis in patients receiving NEUPOGEN is unknown. The occurrence of Sweetu2019s syndrome (acute febrile dermatosis) has been reported occasionally. However, since a significant percentage of these patients were suffering from leukaemia, a condition known to be associated with Sweetu2019s syndrome, a causal relationship with NEUPOGEN has not been established. Exacerbation of rheumatoid arthritis has been observed in individual cases. Pulmonary adverse effects including interstitial pneumonia, pulmonary oedema, and pulmonary infiltrates have been reported; in some cases, leading to respiratory failure or ARDS (Adult Respiratory Distress Syndrome, an acute lung injury), which may be fatal.

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. Treatment is symptomatic and supportive.