Posology : מינונים

4.2   Posology and method of administration

IVIg therapy should be initiated and monitored under the supervision of a physician experienced in the treatment of immune system disorders.

Posology

The dose and dose regimen are dependent on the indication.
The dose may need to be individualised for each patient dependent on the clinical response. Dose based on body weight may require adjustment in underweight or overweight patients.

The following dose regimens are given as a guidance.

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. 3–6 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 3–4 weeks.

The dose required to achieve a trough level of IgG of 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.


Replacement therapy in secondary immunodeficiencies (as defined in section 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.
Immunomodulation in:
Primary immune thrombocytopenia
There are two alternative treatment schedules:
- 0.8–1 g/kg given on day 1; this dose may be repeated once within 3 days - 0.4 g/kg given daily for 2–5 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 divided over 2 –5 consecutive days
Maintenance doses: 1 g/kg divided 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 physician’s 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 divided 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 physician’s 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 infusions Replacement therapy:

Primary immunodeficiency syndromes           Starting dose:
0.4–0.8 g/kg

Maintenance dose:
0.2–0.8 g/kg             every 3–4 weeks
Secondary immunodeficiencies (as defined in section 4.1)                      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/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:        every 3 weeks in divided
1 g/kg                   doses over 1–2 days
Multifocal Motor Neuropathy (MMN)
Starting dose:
2 g/kg                   in divided doses over 2–5 consecutive days
Maintenance dose:
1 g/kg                   every 2–4 weeks or                       or
2 g/kg                   every 4–8 weeks in divided doses 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 must be 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.


Method of administration
Intravenous use.
Intratect 100 g/l should be infused intravenously at an initial rate of not more than 0.3 ml/kg/h for 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 gradually be increased to a maximum of 1.9 ml/kg/h.

Replacement Therapy:
In patients who have tolerated the infusion rate of 1.9 ml/kg/h well, the rate may be gradually increased to 6 ml/kg/h and if still tolerated well, it may be further increased gradually to a maximum of 8 ml/kg/h.

In general, dosage and infusion rates have to be individually tailored according to the patient's needs (see also section 4.4).