Posology : מינונים

4.2   Posology and method of administration

Neupogen therapy should only be given in collaboration with an oncology center which has experience in G-CSF treatment and hematology and has the necessary diagnostic facilities. The mobilization and apheresis procedures should be performed in collaboration with an oncology-hematology center with acceptable experience in this field and where the monitoring of hematopoietic progenitor cells can be correctly performed.

Established cytotoxic chemotherapy

Posology
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 (see section 6.6). 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 myeloablative therapy followed by bone marrow transplantation 
Posology

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 following 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                                       Neupogen Dose Adjustment 9
> 1.0 × 10 /l for 3 consecutive days                   Reduce to 0.5 MU (5 µg)/kg/day Then, if ANC remains > 1.0 × 109/l for 3 more          Discontinue Neupogen consecutive days
If the ANC decreases to < 1.0 × 109/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 given by continuous 24-hour subcutaneous infusion. Neupogen should be diluted in 20 ml of 5% glucose solution (see section 6.6).

For the mobilization of PBPCs in patients undergoing myelosuppressive or myeloablative therapy followed by autologous PBPC transplantation

Posology

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 × 109/l to > 5.0 × 109/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 (see section 6.6).

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 
Posology

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 × 106 CD34+ cells/kg recipient body weight.

Method of administration

Neupogen should be given by subcutaneous injection.
In patients with severe chronic neutropenia (SCN)

Posology

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 × 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. Subsequently the dose may be individually adjusted every 1 to 2 weeks to maintain the average neutrophil count between 1.5 × 109/l and 10 × 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 ≤ 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.
In patients with HIV infection

Posology

For reversal of neutropenia:
The recommended starting dose of Neupogen is 0.1 MU (1 µg)/kg/day, with titration up to a maximum of 0.4 MU (4 µg)/kg/day until a normal neutrophil count is reached and can be maintained (ANC > 2.0 × 109/l).
In clinical studies, > 90% of patients responded at these doses, achieving reversal of neutropenia in a median of 2 days.

In a small number of patients (< 10%), doses up to 1.0 MU (10 µg)/kg/day were required to achieve reversal of neutropenia.

For maintaining normal neutrophil counts:
When reversal of neutropenia has been achieved, the minimal effective dose to maintain a normal neutrophil count should be established. Initial dose adjustment to alternate day dosing with 30 MU (300 µg)/day is recommended. Further dose adjustment may be necessary, as determined by the patient's ANC, to maintain the neutrophil count at > 2.0 × 109/l. In clinical studies, dosing with 30 MU (300 µg)/day on 1 to 7 days per week was required to maintain the ANC > 2.0 × 109/l, with the median dose frequency being 3 days per week. Long-term administration may be required to maintain the ANC > 2.0 × 109/l.
Method of administration

Reversal of neutropenia or maintaining normal neutrophil counts: 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.