ACCOFIL

Accofil 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.

5 MU (5 μg)/kg/day. The first dose of Accofil should be administered at least 24 hours after cytotoxic chemotherapy. 4 μg /kg/day) was used. Daily dosing with filgrastim should continue until the expected neutrophil nadir is passed and the neutrophil count has recovered to the normal range.

Following established chemotherapy for solid tumours, lymphomas, and lymphoid leukaemia, it is expected that the duration of treatment required to fulfil these criteria will be up to 14 days. Following induction and consolidation treatment for acute myeloid leukaemia 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 to2 days after initiation of filgrastim therapy. However, for a sustained therapeutic response, filgrastim therapy should not be discontinued before the expected nadir has passed and the neutrophil count has recovered to the normal range.

Premature discontinuation of filgrastim therapy, prior to the time of the expected neutrophil nadir, is not recommended. 0 MU(10 μg)/kg/day The first dose of filgrastim should be administered at least 24 hours following cytotoxic chemotherapy and at least 24 hours after bone marrow infusion.

0 MU (10 μg)/kg/day for 5 to7 consecutive days. Timing of leukapheresis: one or two leukapheresis on days 5 and 6 which is often sufficient. In other circumstances, additional leukapheresis may be necessary. Filgrastim dosing should be maintained until the last leukapheresis.

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. 0 x 109/L. For patients who have not had extensive chemotherapy, one leukapheresis is often sufficient.

In other circumstances, additional leukapheresis are recommended. 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 106 CD34+ cells/kg recipient bodyweight.

2 MU (12 μg)/kg/day as a single dose or in divided doses. 5 MU (5 μg)/kg/day as a single dose or in divided doses. 5 x 109/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. 5 x 109/L and 10 x 109/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 of ≤ 24 μg/kg/day. The long-term safety of administration of filgrastim at doses above 24 μg/kg/day in patients with SCN has not been established. In patients with HIV […]

8. Malignant cell growth Granulocytecolony stimulating factor can promote growth of myeloid cells in vitro and similar effects may be seen on some non-myeloid cells in vitro. Myelodysplastic syndrome or Chronic myeloid leukaemia The safety and efficacy of filgrastim administration in patients with myelodysplastic syndrome or chronic myelogenous leukaemia have not been established.

Filgrastim is not indicated for use in these conditions. Particular care should be taken to distinguish the diagnosis of blast transformation of chronic myeloid leukaemia from acute myeloid leukaemia. Acute myeloid leukaemia In view of limited safety and efficacy data in patients with secondary AML, filgrastim should be administered with caution.

The safety and efficacy of filgrastim administration in de novo AML patients aged < 55 years with good cytogenetics [t (8; 21), t (15; 17), and inv (16)] have not been established. Thrombocytopenia Thrombocytopenia has been reported in patients receiving filgrastim.

Platelet counts should be monitored closely, especially during the first few weeks of filgrastim therapy. Consideration should be given to temporary discontinuation or dose reduction of filgrastim in patients with severe chronic neutropenia who develop thrombocytopenia (platelet count < 100 × 109/l).

Other special precautions Osteoporosis Monitoring of bone density may be indicated in patients with underlying osteoporotic bone diseases who undergo continuous therapy with filgrastim for more than 6 months. 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 dyspnoea in association with radiological signs of pulmonary infiltrates and deterioration in pulmonary function may be preliminary signs of Acute Respiratory Distress Syndrome (ARDS).

Filgrastim should be discontinued and appropriate treatment given. Capillary leak syndrome Capillary leak syndrome, which can be life-threatening if treatment is delayed, has been reported after granulocyte colony-stimulating factor administration, and is characterised by hypotension, hypoalbuminaemia, oedema and haemoconcentration.

8). 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.

Splenomegaly and splenic rupture Generally asymptomatic cases of splenomegaly and cases of splenic rupture have been reported in patients and normal donors following administration of filgrastim. Some cases of splenic rupture were fatal.

g. clinical examination, ultrasound). A diagnosis of splenic rupture should be considered in donors and/or patients reporting left upper abdominal or shoulder tip pain. Dose reductions of Filgrastim have been noted to slow or stop the progression of splenic enlargement in patients with severe chronic neutropenia, and in 3% of patients a splenectomy was required.

3 MU/kg/day (3 μg/kg/day). No undesirable effects directly attributable to this degree of leucocytosis have been reported. However, in view of the potential risks associated with severe leucocytosis, a white blood cell count should be performed at regular intervals during filgrastim therapy.

If leucocyte counts exceed 50 x 109/L after the expected nadir, filgrastim should be discontinued immediately. When administrered for PBPC mobilisation, filgrastim should be discontinued or its dosage should be reduced if the leucocyte counts rise to > 70 x 109/L.

Special precautions in cancer patients Filgrastim 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 tumour 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 filgrastim alone does not preclude thrombocytopenia and anaemia due to myelosuppressive chemotherapy. g. full doses on the prescribed schedule) the patient may be at greater risk of thrombocytopenia and anaemia.

Regular monitoring of platelet count and haematocrit is recommended. Special care should be taken when administering single or combination chemotherapeutic agents which are known to cause severe thrombocytopenia. The use of filgrastim-mobilised PBPCs has been shown to reduce the depth and duration of thrombocytopenia following myelosuppressive or myeloablative chemotherapy.

Myelodysplastic syndrome and acute myeloid leukaemia in breast and lung cancer patients In the post-marketing observational study setting, myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) have been associated with the use of pegfilgrastim, an alternative G-CSF medicine, in conjunction with chemotherapy and/or radiotherapy in breast and lung cancer patients.

A similar association between filgrastim and MDS/AML has not been observed. Nonetheless, patients with breast cancer and patients with lung cancer should be monitored […]

Traceability In order to improve the traceability of granulocyte-colony stimulating factors (G-CSFs), the trade name of the administered product should be clearly recorded in the patient file. Special warning and precautions across indications Hypersensitivity Hypersensitivity, including anaphylactic reactions, occurring on initial or subsequent treatment have been reported in patients treated with filgrastim.

Permanently discontinue filgrastim in patients with clinically significant hypersensitivity. Do not administer filgrastim to patients with a history of hypersensitivity to filgrastim or pegfilgrastim. Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity.

Rates of generation of antibodies against filgrastim is generally low. Binding antibodies do occur as expected with all biologics; however, they have not been associated with neutralising activity at present. Aortitis Aortitis has been reported after G-CSF administration in healthy subjects and in cancer patients.

g. C-reactive protein and white blood cell count). In most cases aortitis was diagnosed by CT scan and generally resolved after withdrawal of G-CSF. 8. Malignant cell growth Granulocytecolony stimulating factor can promote growth of myeloid cells in vitro and similar effects may be seen on some non-myeloid cells in vitro.

Myelodysplastic syndrome or Chronic myeloid leukaemia The safety and efficacy of filgrastim administration in patients with myelodysplastic syndrome or chronic myelogenous leukaemia have not been established. Filgrastim is not indicated for use in these conditions.

Particular care should be taken to distinguish the diagnosis of blast transformation of chronic myeloid leukaemia from acute myeloid leukaemia. Acute myeloid leukaemia In view of limited safety and efficacy data in patients with secondary AML, filgrastim should be administered with caution.

The safety and efficacy of filgrastim administration in de novo AML patients aged < 55 years with good cytogenetics [t (8; 21), t (15; 17), and inv (16)] have not been established. Thrombocytopenia Thrombocytopenia has been reported in patients receiving filgrastim.

Platelet counts should be monitored closely, especially during the first few weeks of filgrastim therapy. Consideration should be given to temporary discontinuation or dose reduction of filgrastim in patients with severe chronic neutropenia who develop thrombocytopenia (platelet count < 100 × 109/l).

Other special precautions Osteoporosis Monitoring of bone density may be indicated in patients with underlying osteoporotic bone diseases who undergo continuous therapy with filgrastim for more than 6 months. 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 dyspnoea in association with radiological signs of pulmonary infiltrates and deterioration in pulmonary function may be preliminary signs of Acute Respiratory Distress Syndrome (ARDS).

Filgrastim should be discontinued and appropriate treatment given. Capillary leak syndrome Capillary leak syndrome, which can be life-threatening if treatment is delayed, has been reported after granulocyte colony-stimulating factor administration, and is characterised by hypotension, hypoalbuminaemia, oedema and haemoconcentration.

8). 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.

Splenomegaly and splenic rupture Generally asymptomatic cases of splenomegaly and cases of splenic rupture have been reported in patients and normal donors following administration of filgrastim. Some cases of splenic rupture were fatal.

g. clinical examination, ultrasound). A diagnosis of splenic rupture should be considered in donors and/or patients reporting left upper abdominal or shoulder tip pain. Dose reductions of Filgrastim have been noted to slow or stop the progression of splenic enlargement in patients with severe chronic neutropenia, and in 3% of patients a splenectomy was required.

3 MU/kg/day (3 μg/kg/day). No undesirable effects directly attributable to this degree of leucocytosis have been reported. However, in view of the potential risks associated with severe leucocytosis, a white blood cell count should be performed at regular intervals during filgrastim therapy.

If leucocyte counts exceed 50 x 109/L after the expected nadir, filgrastim should be discontinued immediately. When administrered for PBPC mobilisation, filgrastim should be discontinued or its dosage should be reduced if the leucocyte counts rise to > 70 x 109/L.

Special precautions in cancer patients Filgrastim 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 tumour 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 […]

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