Posology : מינונים

4.2   Posology and method of administration
Replacement therapy should be initiated and monitored under the supervision of a physician experienced in the treatment of immunodeficiency.
Posology
The dose and dosage regimen is dependent on the indication.
In replacement therapy the dosage may need to be individualised for each patient dependent on the pharmacokinetic and clinical response. The following dosage regimens are given as a guideline.

Replacement therapy in primary immunodeficiency syndromes
The dosage regimen should achieve a trough level of IgG (measured before the next infusion) of at least 5 - 6 g/l. Three to six months are required after the initiation of therapy for equilibration to occur. The recommended starting dose is 0.4 - 0.8 g/kg given once followed by at least 0.2 g/kg every three to four weeks.
The dose required to achieve a trough level of 5 - 6 g/l is of the order of 0.2 - 0.8 g/kg/month.
The dosage interval when steady state has been reached varies from 3 - 4 weeks.

Trough levels should be measured and assessed in conjunction with the incidence of infection.
To reduce the rate of infection, it may be necessary to increase the dosage and aim for higher trough levels.

Hypogammaglobulinaemia and recurrent bacterial infections in patients with chronic lymphocytic leukaemia, in whom prophylactic antibiotics have failed,
hypogammaglobulinaemia and recurrent bacterial infections in plateau phase multiple myeloma patients who have failed to respond to pneumococcal immunisation; congenital AIDS with recurrent bacterial infections.

The recommended dose is 0.2 - 0.4 g/kg every three to four weeks.

Primary immune thrombocytopenic
There are two alternative treatment schedules:
0.8 - 1 g/kg given on day one, which may be repeated once within 3 days, or 0.4 g/kg given daily for two to five days. The treatment can be repeated if relapse occurs.

Guillain Barré syndrome
0.4 g/kg/day over 5 days.

Kawasaki disease
1.6 - 2.0 g/kg should be administered in divided doses over two to five days or 2.0 g/kg as a single dose.
Patients should receive concomitant treatment with acetylsalicylic acid.

Allogeneic bone marrow transplantation
Human normal immunoglobulin treatment can be used as part of the conditioning regimen and after the transplant.
For the treatment of infections and prophylaxis of graft versus host disease, dosage is individually tailored. The starting dose is normally 0.5 g/kg/week, starting seven days before transplantation and for up to 3 months after transplantation.
In case of persistent lack of antibody production, dosage of 0.5 g/kg/month is recommended until antibody level returns to normal.

The dosage recommendations are summarised in the following table:

Indication                       Dose                        Frequency 
Replacement therapy in           - starting dose: primary immunodeficiency         0.4 - 0.8 g/kg
- thereafter:               every 2 - 4 weeks to obtain IgG
0.2 - 0.8 g/kg              trough level of at least 4 - 6 g/l

Replacement therapy in     0.2 - 0.4 g/kg                    every 3 - 4 weeks to obtain IgG secondary immunodeficiency                                   trough level of at least 5 - 6 g/l 
Congenital AIDS                  0.2 - 0.4 g/kg              every 3 - 4 weeks Immunomodulation:

Primary immune                   0.8 - 1 g/kg                on day 1, possibly repeated once thrombocytopenic                 or                          within 3 days 
0.4 g/kg/d                  for 2 - 5 days

Guillain Barré syndrome          0.4 g/kg/d                  for 5 days 
Kawasaki disease                 1.6 - 2 g/kg                in divided doses over or                          2 - 5 days in association with acetylsalicylic acid

2 g/kg                      in one dose in association with acetylsalicylic acid

Paediatric population
Flebogamma 5% DIF is contraindicated in children aged 0 to 2 years (see section 4.3).

The posology in children and adolescents (2 - 18 years) is not different to that of adults as the posology for each indication is given by body weight and adjusted to the clinical outcome of the above mentioned conditions.


Method of administration
Flebogamma 5% DIF should be infused intravenously at an initial rate of 0.01 - 0.02 ml/kg/min for the first thirty minutes. If well tolerated, (see section 4.4), the rate of administration may gradually be increased to a maximum of 0.1 ml/kg/min.