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. Treatment at home should be similarly supervised, with the patient fully assessed and trained in hospital prior to self-infusion at home.

Posology

The dose and dose regimen is 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 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 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 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 - 2.0 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.

The dosage 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 
Congenital AIDS                       0.2 - 0.4 g/kg     every 3 - 4 weeks Immunomodulation:

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

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


Paediatric population
The posology in children and adolescents 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.
Gammaplex should be infused intravenously, at an initial rate of 0.01 - 0.02 ml/kg/minute (0.6 - 1.2 ml/kg/hour) for 15 minutes. If well tolerated (see section 4.4), the rate of administration may be increased to 0.04 ml/kg/minute (2.4 ml/kg/hour) for 15 minutes, then to 0.06 ml/kg/minute (3.6 ml/kg/hour) for 15 minutes, followed by a maximum of 0.08 ml/kg/minute (4.8 ml/kg/hour).