NEUPOGEN PRE-FILLED SYRINGE 30 MU/0.5 ML [SIN10780P]

Product Info

NEUPOGEN PRE-FILLED SYRINGE 30 MU/0.5 ML

[SIN10780P]

2.1 Therapeutic Indication(s)

Established cytotoxic chemotherapy
Neupogen is indicated for 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 considered to be at increased risk of prolonged severe neutropenia (see section 2.5.3 Paediatric Use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Peripheral blood progenitor cell mobilisation (PBPC)
Neupogen is indicated for the mobilisation of autologous peripheral blood progenitor cells alone, or following myelosuppressive chemotherapy and the mobilisation of peripheral blood progenitor cells in normal donors (allogeneic PBPC).

Severe chronic neutropenia (SCN)
Long-term administration of Neupogen is indicated in patients, children or adults, with severe congenital, cyclic or idiopathic neutropenia with an Absolute Neutrophil Count (ANC) ≤ 0.5 x 10⁹/l, and a history of severe or recurrent infections, to increase neutrophil counts and to reduce the incidence and duration of infection-related events.

HIV infection
Neupogen is indicated for the treatment of persistent neutropenia (ANC ≤ 1.0 x 10⁹/l) in patients with advanced HIV infection, in order to reduce the risk of bacterial infections, when other options to manage neutropenia are inappropriate.

2.2 Dosage and Administration

Neupogen therapy should only be given in collaboration with an oncology center 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 center with acceptable experience in this field and where the monitoring of haematopoietic progenitor cells can be correctly performed.

Established cytotoxic chemotherapy
The recommended dose of Neupogen is 0.5 million units (5 mcg)/kg/day. The first dose of Neupogen should not be administered less than 24 hours following cytotoxic chemotherapy. 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 4.2 Special Instructions for Use, Handling and Disposal – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). 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 circumstances.

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 leukaemia, 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 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.

For use in children see section 2.5.3 Paediatric Use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

In patients treated with myeloablative therapy followed by bone marrow transplantation
The recommended starting dose of Neupogen is 1.0 million units (10 mcg)/kg/day given as a 30 minute or 24 hour intravenous infusion or 1.0 million units (10 mcg)/kg/day given by continuous 24 hours subcutaneous infusion.

Neupogen should be diluted in 20 ml of 5% glucose solution (see section 4.2 Special Instructions for Use, Handling and Disposal – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

The first dose of Neupogen should not be administered less than 24 hours following 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.

Once the neutrophil nadir has been passed, the daily dose of Neupogen should be titrated against the neutrophil response as follows (see also section 2.5.3 Paediatric Use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information):

Peripheral blood progenitor cell mobilisation

Mobilisation of Peripheral Blood Progenitor Cells (PBPC) in patients undergoing myelosuppressive or myeloablative therapy followed by autologous peripheral blood progenitor cell transplantation with or without bone marrow transplantation

The recommended dose of Neupogen for PBPC mobilisation when used alone is 1.0 million units (10 mcg)/kg/day as a 24 hour subcutaneous continuous infusion or a single daily subcutaneous injection for 5 to 7 consecutive days. For infusions Neupogen should be diluted in 20 ml of 5% glucose solution (see section 4.2 Special Instructions for Use, Handling and Disposal – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Timing of leukapheresis: one or two leukaphereses on days 5 and 6 are often sufficient. In other circumstances, additional leukaphereses may be necessary. Neupogen dosing should be maintained until the last leukapheresis.

The recommended dose of Neupogen for PBPC mobilisation after myelosuppressive chemotherapy is 0.5 million units (5 mcg)/kg/day given daily by subcutaneous injection 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 10⁹/l to > 5.0 x 10⁹/l. For patients who have not had extensive chemotherapy, one leukapheresis is often sufficient. In other circumstances, additional leukaphereses are recommended.

Mobilisation of Peripheral Blood Progenitor Cells (PBPC) in normal donors prior to allogeneic peripheral blood progenitor cell transplantation

For PBPC mobilisation in normal donors, Neupogen should be administered at 10 mcg/kg/day subcutaneously 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 recipients bodyweight.

Severe chronic neutropenia (SCN)

Congenital neutropenia: The recommended starting dose is 1.2 million units (12 mcg)/kg/day subcutaneously as a single dose or in divided doses.

Idiopathic or cyclic neutropenia: The recommended starting dose is 0.5 million units (5 mcg)/kg/day subcutaneously 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 mcg/kg/day.

The long-term safety of Neupogen administration above 24 mcg/kg/day in patients with severe chronic neutropenia has not been established.

For children see section 2.5.3 Paediatric Use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

HIV infection

For Reversal of Neutropenia:
The recommended starting dose of Neupogen is 0.1 million units (1 mcg)/kg/day given daily by subcutaneous injection with titration up to a maximum of 0.4 million units (4 mcg)/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 million units (10 mcg)/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 million units (300 mcg)/day by subcutaneous injection 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 million units (300 mcg)/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.

2.2.1 Special Dosage Instructions
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 (see section 2.5.4 Geriatric Use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

The dosage recommendations in paediatric patients are the same as those in adults receiving myelosuppressive cytotoxic chemotherapy (see section 2.5.3 Paediatric Use – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

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.

2.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 1.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.