Posology : מינונים

4.2 Posology and method of administration                                                Mozobil may influence the ability to drive and use machines. Some patients have
experienced dizziness, fatigue or vasovagal reactions; therefore caution is advised
Mozobil therapy should be initiated and supervised by a physician experienced            when driving or operating machines.
in oncology and/or haematology. The mobilisation and apheresis procedures
should be performed in collaboration with an oncology haematology centre with            4.8 Undesirable effects
acceptable experience in this field and where the monitoring of haematopoietic           Summary of the safety profile
progenitor cells can be correctly performed.                                             Safety data for Mozobil in conjunction with G-CSF in oncology patients with
Posology                                                                                 lymphoma and multiple myeloma were obtained from 2 placebo-controlled
The recommended daily dose of plerixafor by subcutaneous injection (SC) is:              Phase III studies (301 patients) and 10 uncontrolled Phase II studies (242 patients).
• 20 mg fixed dose or 0.24 mg/kg of body weight for patients weighing ≤ 83 kg            Patients were primarily treated with daily doses of 0.24 mg/kg plerixafor by (see section 5.2).                                                                  subcutaneous injection. The exposure to plerixafor in these studies ranged from 1
• 0.24 mg/kg of body weight for patients weighing > 83 kg.                               to 7 consecutive days (median = 2 days). It should be administered by subcutaneous injection 6 to 11 hours prior to               In the two Phase III studies in non-Hodgkin’s lymphoma and multiple myeloma
initiation of each apheresis following 4 day pre-treatment with granulocyte-             patients (AMD3100-3101 and AMD3100-3102, respectively), a total of 301 patients
colony stimulating factor (G-CSF). In clinical trials, Mozobil has been commonly         were treated in the Mozobil and G-CSF group and 292 patients were treated in
used for 2 to 4 (and up to 7) consecutive days.                                          the placebo and G-CSF group. Patients received daily morning doses of G-CSF
The weight used to calculate the dose of plerixafor should be obtained within 1          10 µg/kg for 4 days prior to the first dose of plerixafor or placebo and on each
week before the first dose of plerixafor. In clinical studies, the dose of plerixafor    morning prior to apheresis. Adverse reactions that occurred more frequently
has been calculated based on body weight in patients up to 175% of ideal body            with Mozobil and G-CSF than placebo and G-CSF and were reported as related
weight. Plerixafor dose and treatment of patients weighing more than 175%                in ≥1% of the patients who received Mozobil, during haematopoietic stem cell
of ideal body weight have not been investigated. Ideal body weight can be                mobilisation and apheresis and prior to chemotherapy/ablative treatment in
determined using the following equations:                                                preparation for transplantation are shown in Table 1.
male (kg):                          50 + 2.3 x ((Height (cm) x 0.394) – 60);          From chemotherapy/ablative treatment in preparation of transplantation through
female (kg):                        45.5 + 2.3 x ((Height (cm) x 0.394) – 60).        12 months post transplantation, no significant differences in the incidence of
adverse reactions were observed across treatment groups.
Based on increasing exposure with increasing body weight, the plerixafor dose            Tabulated list of adverse reactions
should not exceed 40 mg/day.                                                             Adverse reactions are listed by System Organ Class and frequency. Frequencies
Recommended concomitant medicinal products                                               are defined according to the following convention: very common (≥ 1/10);
In pivotal clinical studies supporting the use of Mozobil, all patients received daily   common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000
morning doses of 10 µg/kg G-CSF for 4 consecutive days prior to the first dose of        to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the
plerixafor and on each morning prior to apheresis.                                       available data).
Special populations                                                                      Table 1. Adverse reactions occurring more frequently with Mozobil than
Renal impairment                                                                         placebo and considered related to Mozobil during mobilisation and
Patients with creatinine clearance 20-50 ml/min should have their dose of                apheresis in phase III studies
plerixafor reduced by one-third to 0.16 mg/kg/day (see section 5.2). Clinical data        Blood and lymphatic system disorders
with this dose adjustment are limited. There is insufficient clinical experience
to make alternative posology recommendations for patients with a creatinine                                           Not known Splenomegaly, splenic rupture (see section
clearance <20 ml/min, as well as to make posology recommendations for patients                                                  4.4)**
on haemodialysis.                                                                         Immune system disorders
Based on increasing exposure with increasing body weight the dose should not                                          Uncommon Allergic reaction*
exceed 27 mg/day if the creatinine clearance is lower than 50 ml/min.                                                                  Anaphylactic reactions, including
Paediatric population                                                                                                                  anaphylactic shock (see section
The experience in paediatric patients is limited. The safety and efficacy of Mozobil                                                   4.4) **
in paediatric patients have not been established in controlled clinical studies.          Psychiatric disorders
Elderly patients (> 65 years old)                                                                                        Common Insomnia
No dose modifications are necessary in elderly patients with normal renal
function. Dose adjustment in elderly patients with creatinine clearance ≤ 50                                          Uncommon Abnormal dreams, nightmares
ml/min is recommended (see Renal impairment above). In general, care should               Nervous system disorders
be taken in dose selection for elderly patients due to the greater frequency of                                          Common Dizziness, headache
decreased renal function with advanced age.
Gastrointestinal disorders
Method of administration                                                                                            Very common Diarrhoea, nausea
For subcutaneous injection. Each vial of Mozobil is intended for single use only.
Common Vomiting, abdominal pain, stomach
Vials should be inspected visually prior to administration and not used if there
discomfort, dyspepsia, abdominal
is particulate matter or discolouration. Since Mozobil is supplied as a sterile,
distention, constipation, flatulence,
preservative-free formulation, aseptic technique should be followed when
hypoaesthesia oral, dry mouth
transferring the contents of the vial to a suitable syringe for subcutaneous
administration (see section 6.3).                                                         Skin and subcutaneous tissue disorders
Common Hyperhidrosis, erythema