ZARZIO

6). 0 MU/kg/day (10 μg/kg/day) for 5 - 7 consecutive days. Timing of leukapheresis: 1 or 2 leukaphereses on days 5 and 6 are often sufficient. In other circumstances, additional leukaphereses may be necessary. Filgrastim dosing should be maintained until the last leukapheresis.

5 MU/kg/day (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 leukaphereses are recommended.

Method of administration Filgrastim for PBPC mobilisation when used alone:

Filgrastim may be given as a 24 hour subcutaneous continuous infusion or subcutaneous injection. 6).

Filgrastim for PBPC mobilisation after myelosuppressive chemotherapy:

Filgrastim should be given by subcutaneous injection. 0 MU/kg/day (10 μg/kg/day) for 4 - 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.

Method of administration Filgrastim should be given by subcutaneous injection. 2 MU/kg/day (12 μg/kg/day) as a single dose or in divided doses. 5 MU/kg/day (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 1 - 2 weeks of therapy, the initial dose may be doubled or […]

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 for signs and symptoms of MDS/AML. Other special precautions The effects of filgrastim in patients with substantially reduced myeloid progenitors have not been studied.

Filgrastim 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 tumour).

Vascular disorders, including veno-occlusive disease and fluid volume disturbances, have been reported occasionally in patients undergoing high dose chemotherapy followed by transplantation. 1). Increased haematopoietic 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 mobilisation Mobilisation There are no prospectively randomised comparisons of the two recommended mobilisation methods (Filgrastim 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 mobilisation method should be considered in relation to the overall objectives of treatment for an individual patient.

0 x 106 CD34+ cells/kg) or acceleration of platelet recovery to the same degree. Some cytotoxic agents exhibit particular toxicities to the haematopoietic progenitor pool and may adversely affect progenitor mobilisation. Agents such as melphalan, carmustine (BCNU) and carboplatin, when administered over prolonged periods prior to attempts at progenitor mobilisation may reduce progenitor yield.

However, the administration of melphalan, carboplatin or BCNU together with filgrastim has been shown to be effective for progenitor mobilisation. When a PBPC transplantation is envisaged it is advisable to plan the stem cell mobilisation procedure early in the treatment course of the patient.

Particular attention should be paid to the number of progenitors mobilised in such patients before the administration of high-dose chemotherapy. If yields are inadequate, as measured by the criteria above, alternative forms of treatment not requiring progenitor support should be considered.

Assessment of progenitor cell yields In assessing the number of progenitor cells harvested in patients treated with filgrastim, particular attention should be paid to the method of quantitation. The results of flow cytometric analysis of CD34+ cell numbers vary depending on the precise methodology used and, recommendations of numbers based on studies in other laboratories need to be interpreted with caution.

Statistical analysis of the relationship between the number of CD34+ cells re-infused and the rate of platelet recovery after high-dose chemotherapy indicates a complex but continuous relationship. 0 x 106 CD34+ cells/kg is based on […]

g. clinical examination, ultrasound). A diagnosis of splenic rupture should be considered in donors and/or patients reporting left upper abdominal pain 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.

Malignant cell growth Granulocyte colony stimulating factor (G-CSF) 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 acute myelogenous leukaemia (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 x 109/l).

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

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

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. Special warnings and precautions associated with co-morbidities Special precautions in sickle cell trait and sickle cell disease Sickle cell crises, in some cases fatal, have been reported with the use of filgrastim in patients with sickle cell trait or sickle cell disease.

Physicians should use caution when prescribing filgrastim 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 filgrastim for more than 6 months.

Special precautions in cancer patients Filgrastim should not be used to increase the dose of cytotoxic chemotherapy beyond established dosage […]