2
Human normal immunoglobulin contains mainly immunoglobulin G (IgG) with a broad spectrum of antibodies against infectious agents.
Human normal immunoglobulin contains the IgG antibodies present in the normal population. It is usually prepared from pooled plasma from not fewer than 1000 donations. It has a distribution of immunoglobulin G subclasses closely proportional to that in native human plasma. Adequate doses of this medicinal product may restore abnormally low immunoglobulin G levels to the normal range.
The mechanism of action in indications other than replacement therapy is not fully elucidated, but includes immunomodulatory effects.
Paediatric population
There are no theoretical or observed differences in the action of immunoglobulins in children compared to adults.
5.2 Pharmacokinetic properties
Human normal immunoglobulin is immediately and completely bioavailable in the recipient's circulation after intravenous administration. It is distributed relatively rapidly between plasma and extravascular fluid; after approximately 3 to 5 days equilibrium is reached between the intra- and extravascular compartments.
Pharmacokinetic parameters for KIOVIG were determined in the two clinical studies in PID patients performed in Europe and the US. In these studies, a total of 83 subjects at least 2 years of age were treated with doses of 300 to 600 mg/kg body weight every 21 to 28 days for 6 to 12 months. The median IgG half-life after administration of KIOVIG was 32.5 days. This half-life may vary from patient to patient, in particular in primary immunodeficiency. Pharmacokinetic parameters for the product are summarized in the table below. All parameters were analysed separately for three age groups, children (below 12 years, n=5), adolescents (13 to 17 years, n=10), and adults (above 18 years of age, n=64). The values obtained in the studies are comparable to parameters reported for other human immunoglobulins.
Summary of KIOVIG pharmacokinetic parameters
Parameter
Children
(12 years or below)
Adolescents
(13 to 17 years)
Adults
(18 years or above)
Median
95% CI*
Median
95% CI
Median
95% CI
Terminal half-life (days)
41.3
20.2 to 86.8
45.1
27.3 to 89.3
31.9
29.6 to 36.1
Cmin (mg/dl)/(mg/kg)
(trough level)
2.28
1.72 to 2.74
2.25
1.98 to 2.64
2.24
1.92 to 2.43
Cmax (mg/dl)/(mg/kg)
(peak level)
4.44
3.30 to 4.90
4.43
3.78 to 5.16
4.50
3.99 to 4.78
In-vivo recovery (%)
121
87 to 137
99
75 to 121
104
96 to 114
Incremental recovery (mg/dl)/(mg/kg)
2.26
1.70 to 2.60
2.09
1.78 to 2.65
2.17
1.99 to 2.44
AUC0-21d (g·h/dl) (area under the curve)
1.49
1.34 to 1.81
1.67
1.45 to 2.19
1.62
1.50 to 1.78
*CI – Confidence Interval
IgG and IgG-complexes are broken down in cells of the reticuloendothelial system.
5.3 Preclinical safety data
Immunoglobulins are normal constituents of the human body.
The safety of KIOVIG has been demonstrated in several non-clinical studies. Non-clinical data reveal no special risk for humans based on conventional studies of safety pharmacology and toxicity.
Studies of repeated dose toxicity, genotoxicity, and toxicity to reproduction in animals are impracticable due to induction of and interference by developing antibodies to heterologous proteins. Since clinical experience provides no evidence for carcinogenic potential of immunoglobulins, no experimental studies in hetero |
