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 dose regimen are dependent on the indication.
In replacement therapy the dose may need to be individualised for each patient dependent on the pharmacokinetic and clinical response.

The following dose regimens are given as a guideline.

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

IgG trough levels should be measured and assessed in conjunction with the incidence of infection. To reduce the rate of bacterial infection, it may be necessary to increase the dose 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 to pneumococcal immunisation; children and adolescents with congenital AIDS and recurrent bacterial infections
The recommended dose is 0.2-0.4 g/kg every three to four weeks.

Hypogammaglobulinaemia in patients after allogeneic haematopoietic stem cell transplantation
The recommended dose is 0.2-0.4 g/kg every three to four weeks. The trough levels should be maintained above 5 g/l.


Primary immune thrombocytopenia
There are two alternative treatment schedules:
•     0.8-1 g/kg given on day one; this dose may be repeated once within 3 days
•     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 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.

The dose recommendations are summarised in the following table:

Indication                                    Dose                 Frequency of injections Replacement    therapy       in     primary - starting dose: immunodeficiency                            0.4 – 0.8 g/kg
- thereafter:           every 3 – 4 weeks to obtain IgG
0.2 – 0.8 g/kg          trough level of at least 5 – 6 g/l

Replacement therapy         in    secondary 0.2 – 0.4 g/kg          every 3 – 4 weeks to obtain IgG immunodeficiency                                                    trough level of at least 5 – 6 g/L 
Children and adolescents with AIDS           0.2 – 0.4 g/kg         every 3 – 4 weeks 
Hypogammaglobulinaemia (< 4 g/L) in          0.2 – 0.4 g/kg         every 3 – 4 weeks to obtain IgG patients after allogeneic haematopoietic                            trough level above 5g/L stem cell transplantation
Immunomodulation:

Primary immune thrombocytopenia              0.8 – 1 g/kg          on day 1, possibly repeated once within 3 days or
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 for 2 – 5 days in association with acetylsalicylic acid or
2 g/kg               in one dose in association with acetylsalicylic acid

Paediatric population

The posology in children and adolescents (0-18 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
For intravenous use.

Human normal immunoglobulin should be infused intravenously at an initial rate of 0.5 ml/kg BW/hr for 30 minutes. If well tolerated (see section 4.4), the rate of administration may gradually be increased to a maximum of 6 ml/kg BW/hr. Clinical data obtained from a limited number of patients also indicate that adult PID patients may tolerate an infusion rate of up to 8 ml/kg BW/hr. For further precautions for use see section 4.4.

If dilution prior to infusion is required, KIOVIG may be diluted with 5% glucose solution to a final concentration of 50 mg/ml (5% immunoglobulin). For instructions on dilution of the medicinal product before administration, see section 6.6.

Any infusion-related adverse events should be treated by lowering infusion rates or by stopping the infusion.