Posology : מינונים

4.2 Posology and method of administration
Dosage
The dosage and dosage regimen is dependent on the indication. In replacement therapy the dosage may need to be individualized for each patient depending on the clinical response. The following dosage regimens are given as a guideline.

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

Replacement therapy in myelomas or chronic lymphocytic leukaemia with severe secondary hypogammaglobulinaemia and recurrent infections; replacement therapy in children with congenital AIDS and recurrent infections
The recommended dosage is 0.2 to 0.4 g/kg bw every 3 to 4 weeks.

Immune thrombocytopenic purpura
For the treatment of an acute episode, 0.8 to 1 g/kg bw on day one, which may be repeated once within 3 days, or 0.4 g/kg bw daily for 2 to 5 days. The treatment can be repeated if relapse occurs (see also section “Properties/Effects”).

Guillain-Barré syndrome
0.4 g/kg bw/day over 5 days. Experience in children is limited.

Kawasaki disease
1.6 to 2.0 g/kg bw should be administered in divided doses over 2 to 5 days or 2.0 g/kg bw as a single dose. Patients should receive concomitant treatment with acetylsalicylic acid.

Chronic inflammatory demyelinating polyneuropathy (CIDP)
The recommended starting dose is 2 g/kg bw divided over 2 to 5 consecutive days followed by maintenance doses of 1 g/kg bw given on one day or divided over 2 consecutive days every 3 weeks. The long-term therapy over 24 weeks depends on the patient`s response to the maintenance therapy. The lowest effective maintenance dose and the dosage regimen are to adjust according to the individual course of the disease.

Allogeneic bone marrow transplantation
Human immunoglobulin therapy can be used as part of the conditioning regimen and after transplantation. To treat infections and prevent graft-versus-host disease, the dosage should be individually adjusted.
The starting dosage is usually 0.5 g/kg bw/week, commencing seven days before the transplant.
The treatment is continued for up to 3 months after the transplant. If the lack of antibody production persists, a dosage of 0.5 g/kg bw/month is recommended until IgG antibody levels return to normal.
The dosages recommendations are summarised in the following table:

Indications                                Dose                Intervals between injections Replacement therapy in primary immunodeficiency diseases          – starting dose:
0.4-0.8 g/kg bw
– thereafter:       every 3-4 weeks to obtain IgG
0.2-0.8 g/kg bw   trough levels of at least 5-6 g/l
 secondary immunodeficiency diseases        0.2-0.4 g/kg bw     every 3-4 weeks to obtain IgG trough levels of at least 5-6 g/l
 children with congenital HIV infection     0.2-0.4 g/kg bw     every 3-4 weeks and recurrent infections
Immunomodulation
Immune thrombocytopenic purpura            0.8-1 g/kg bw       on the first day; the therapy may be repeated once within 3 days
 or
0.4 g/kg bw/day     over 2-5 days

Guillain-Barré syndrome                    0.4 g/kg bw/day     over 5 days 

Kawasaki disease                           1.6-2 g/kg bw       divided into several doses given over 2-5 days in conjunction with acetylsalicylic acid or
2 g/kg bw           as a single dose in conjunction with acetylsalicylic acid

Chronic inflammatory demyelinating         starting dose:      in divided doses over 2-5 days polyneuropathy (CIDP)
2 g/kg bw

 maintenance dose:   every 3 weeks over 1-2 days
1 g/kg bw
Allogeneic bone marrow transplantation
– treatment of infections and prevention 0.5 g/kg bw           weekly, from day 7 before of graft-versus-host disease                                 up to 3 months after the transplant
– persistent lack of antibody production
0.5 g/kg bw         monthly, until antibody levels return to normal
 bw = body weight

Use of the product in paediatric population
In the phase III pivotal study on patients with primary immunodeficiency diseases (n=80),19 patients between 3 and 11 years of age and 15 patients from 12 up to and including 18 years of age were treated. In an extension study of patients with primary immunodeficiency diseases (n=55), 13 patients between 3 and 11 years of age and 11 between 12 and including 18 years of age were treated.
In a clinical study on 57 patients with chronic immune thrombocytopenic purpura, 2 paediatric patients (15 and 16 years of age) were treated.
No dose adjustment for children was required in these three studies.
Literature reports indicate that intravenous immunoglobulins are effective in children with CIDP.
However, no data is available on Privigen in this respect.

Method of administration
Privigen should be infused intravenously.

Rate of infusion
The product should initially be infused at a rate of 0.3 ml/kg bw/hr (for approximately 30 min). If well tolerated, the infusion rate can be gradually increased to 4.8 ml/kg bw/hr. In patients with immunodeficiency syndrome who have tolerated substitution treatment with Privigen well, the infusion rate may be gradually increased to a maximal value of 7.2 ml/kg bw/hr.