PLERIXAFOR SEACROSS

Plerixafor Seacross therapy should be initiated and supervised by a physician experienced in oncology and/or haematology. 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.

Age over 60 and/or prior myelosuppressive chemotherapy and/or extensive prior chemotherapy and/or a peak circulating stem cell count of less than 20 stem cells/microliter, have been identified as predictors of poor mobilisation. 2).

24 mg/kg of body weight for patients weighing > 83 kg. 1). 2 ml of 20 mg/ml plerixafor aqueous solution for injection containing 24 mg of plerixafor. Plerixafor Seacross has to be drawn up into a syringe size type which should be selected according to the weight of the patient.

For low weight patients, up to 45 kg of body weight, 1 ml syringes for use in infant patients can be used. 01 ml and therefore is suitable to administer plerixafor, at a dose of 240 μg/kg, to paediatric patients of at least 9 kg body weight.

1 ml to be measured can be used. It should be administered by subcutaneous injection 6 to 11 hours prior to initiation of each apheresis following 4 day pre-treatment with G-CSF. In clinical trials, Plerixafor has been commonly used for 2 to 4 (and up to 7) consecutive days.

The weight used to calculate the dose of plerixafor should be obtained within 1 week before the first dose of plerixafor. In clinical studies, the dose of plerixafor has been calculated based on body weight in patients up to 175% of ideal body weight.

Plerixafor dose and treatment of patients weighing more than 175% of ideal body weight have not been investigated. 394) – 60). Based on increasing exposure with increasing body weight, the plerixafor dose should not exceed 40 mg/day.

Recommended concomitant medicinal products In pivotal clinical studies supporting the use of plerixafor, all patients received daily morning doses of 10 μg/kg G-CSF for 4 consecutive days prior to the first dose of plerixafor and on each morning prior to apheresis.

2). Clinical data with this dose adjustment are limited. There is insufficient clinical experience to make alternative posology recommendations for patients with a creatinine clearance < 20 ml/min, as well as to make posology recommendations for patients on haemodialysis.

Summary of the safety profile Safety data for plerixafor in conjunction with G-CSF in oncology patients with lymphoma and multiple myeloma were obtained from 2 placebo-controlled Phase III studies (301 patients) and 10 uncontrolled Phase II studies (242 patients).

24 mg/kg plerixafor by subcutaneous injection. The exposure to plerixafor in these studies ranged from 1 to 7 consecutive days (median = 2 days). In the two Phase III studies in non-Hodgkin’s lymphoma and multiple myeloma patients (AMD3100-3101 and AMD3100-3102, respectively), a total of 301 patients were treated in the plerixafor and G-CSF group and 292 patients were treated in the placebo and G-CSF group.

Patients received daily morning doses of G-CSF 10 μg/kg for 4 days prior to the first dose of plerixafor or placebo and on each morning prior to apheresis. Adverse reactions that occurred more frequently with plerixafor and G- CSF than placebo and G-CSF and were reported as related in ≥ 1% of the patients who received plerixafor, during haematopoietic stem cell mobilisation and apheresis and prior to chemotherapy/ablative treatment in preparation for transplantation are shown in Table 1.

From chemotherapy/ablative treatment in preparation of transplantation through 12 months post-transplantation, no significant differences in the incidence of adverse reactions were observed across treatment groups. Tabulated list of adverse reactions Adverse reactions are listed by System Organ Class and frequency.

Frequencies are defined according to the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data).

Table 1. 4) ** Psychiatric disorders Common Insomnia Uncommon Abnormal dreams, nightmares Nervous system disorders Common Dizziness, headache Gastrointestinal disorders Very common Diarrhoea, nausea Common Vomiting, abdominal pain, stomach discomfort, dyspepsia, abdominal distention, constipation, flatulence, hypoaesthesia oral, dry mouth Skin and subcutaneous tissue disorders Common Hyperhidrosis, erythema Musculoskeletal and connective tissue disorders * The frequency of allergic reactions presented is based on adverse reactions that occurred in the oncology studies (679 patients).

Tumour cell mobilisation in patients with lymphoma and multiple myeloma When Plerixafor Seacross is used in conjunction with G-CSF for haematopoietic stem cell mobilisation in patients with lymphoma or multiple myeloma‚ tumour cells may be released from the marrow and subsequently collected in the leukapheresis product.

Results showed that, in case tumour cells are mobilised, the number of tumour cells mobilised is not increased upon Plerixafor Seacross plus G-CSF compared to G-CSF alone. Tumour cell mobilisation in leukaemia patients In a compassionate use programme, plerixafor and G-CSF have been administered to patients with acute myelogenous leukaemia and plasma cell leukaemia.

In some instances, these patients experienced an increase in the number of circulating leukaemia cells. For the purpose of haematopoietic stem cell mobilisation, plerixafor may cause mobilisation of leukaemic cells and subsequent contamination of the apheresis product.

Therefore, plerixafor is not recommended for haematopoietic stem cell mobilisation and harvest in patients with leukaemia. Haematological effects Hyperleukocytosis Administration of Plerixafor Seacross in conjunction with G-CSF increases circulating leukocytes as well as haematopoietic stem cell populations.

White blood cell counts should be monitored during plerixafor therapy. Clinical judgment should be exercised when administering plerixafor to patients with peripheral blood neutrophil counts above 50 x 109/L. Thrombocytopenia Thrombocytopenia is a known complication of apheresis and has been observed in patients receiving plerixafor.

Platelet counts should be monitored in all patients receiving plerixafor and undergoing apheresis. 8). , antihistamines, corticosteroids, hydration or supplemental oxygen) or resolved spontaneously. Cases of anaphylactic reactions, including anaphylactic shock, have been reported from world-wide post-marketing experience.

1.