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 is dependent on the indication.
The dose may need to be individualised for each patient dependent on the clinical response. Dose based on bodyweight may require adjustment in underweight or overweight patients.

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 6 g/L or within the normal reference range for the population age. 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 IgG 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.
IgG trough levels should be measured and assessed in conjunction with the incidence of infection.
To reduce the rate of bacterial infections, it may be necessary to increase the dosage and aim for higher trough levels.

Secondary immunodeficiencies (as defined in 4.1.)
The recommended dose is 0.2-0.4 g/kg every three to four weeks.

IgG trough levels should be measured and assessed in conjunction with the incidence of infection.
Dose should be adjusted as necessary to achieve optimal protection against infections, an increase may be necessary in patients with persisting infection; a dose decrease can be considered when the patient remains infection free.


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 (possible repeat of dosing in case of relapse).

Kawasaki disease
2.0 g/kg should be administered as a single dose. Patients should receive concomitant treatment with acetylsalicylic acid.
Chronic inflammatory demyelinating polyneuropathy (CIDP)
Starting dose: 2 g/kg in 2-5 consecutive days
Maintenance doses:
1 g/kg over 1-2 consecutive days every 3 weeks.
The treatment effect should be evaluated after each cycle; if no treatment effect is seen after 6 months, the treatment should be discontinued.
If the treatment is effective long term treatment should be subject to the physicians discretion based upon the patient response and maintenance response. The dosing and intervals may have to be adapted according to the individual course of the disease.

Multifocal Motor Neuropathy (MMN)
Starting dose: 2 g/kg given over 2-5 consecutive days.
Maintenance dose: 1 g/kg every 2 to 4 weeks or 2 g/kg every 4 to 8 weeks.
The treatment effect should be evaluated after each cycle; if no treatment effect is seen after 6 months, the treatment should be discontinued.
If the treatment is effective long term treatment should be subject to the physicians discretion based upon the patient response and maintenance response. The dosing and intervals may have to be adapted according to the individual course of the disease.
The dosage recommendations are summarised in the following table:

Indication                               Dose                         Frequency of injections Replacement therapy
Primary immunodeficiency                  Starting dose: 0.4 - syndromes                                 0.8 g/kg             every 3 - 4 weeks 
Maintenance dose:
0.2- 0.8 g/kg
Secondary Immunodeficiencies (as          0.2 - 0.4 g/kg    every 3 - 4 weeks defined in 4.1.)
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                        2 g/kg                in one dose in association with acetylsalicylic acid

Chronic inflammatory demyelinating       Starting dose: polyradiculoneuropathy (CIDP)            2 g/kg                in divided doses over 2-5 days 
Maintenance dose :
1 g/kg             every 3 weeks over 1-2 days

Multifocal Motor Neuropathy (MMN) Starting dose:
2 g/kg                       over 2-5 consecutive days

Maintenance dose:
1 g/kg            every 2-4 weeks
 or                    or
2 g/kg                every 4-8 weeks over 2-5 days


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.

Hepatic impairment
No evidence is available to require a dose adjustment.

Renal impairment
No dose adjustment unless clinically warranted, see section 4.4.
Elderly
No dose adjustment unless clinically warranted, see section 4.4.


CIDP
Due to the rarity of the disease and consequently the overall low number of patients, only limited experience is available of use of intravenous immunoglobulins in children with CIDP; therefore, only data from literature are available. However, published data are all consistent in showing that the IVIg treatment is equally effective in adults and children, as it is the case for the IVIg established indications.

Method of administration

For intravenous use.
Human normal immunoglobulin should be infused intravenously at an initial rate of 0.46 – 0.92 ml/kg/hr (10 - 20 drops per minute) for 20 - 30 minutes. See section 4.4. In case of adverse reaction, either the rate of administration must be reduced or the infusion stopped. If well tolerated, the rate of administration may be gradually increased to a maximum of 1.85 ml/kg/hr (40 drops/minute).

In PID patients who tolerate the infusion rate of 0.92 ml/kg/hr, the rate of administration may be gradually increased to 2 ml/kg/hr, 4 ml/kg/hr, up to a maximum of 6 ml/kg/hr, every 20-30 minutes and only if the patient tolerates the infusion well.

In general, dosage and infusion rates have to be individually tailored according to the patient's needs. Depending on body weight, dosage and occurrence of adverse reactions, the patient may not reach the maximum infusion speed. In case of adverse reactions, the infusion should be immediately stopped and it should be resumed at the appropriate infusion rate for the patient.

See also paragraph 6.6

Special populations
In paediatric patients (0-18 years) and elderly (> 64 years of age), the initial rate of administration should be 0.46 – 0.92 ml/kg/hr (10 - 20 drops per minute) for 20 - 30 minutes. If well tolerated and considering patient’s clinical conditions, the rate may be gradually increased to a maximum of 1.85 ml/kg/hr (40 drops/minute).