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Pharmacology: Pharmacodynamics: Mechanism of action: 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.
Paediatric population: There are no theoretical or observed differences in the action of immunoglobulins in children compared to adults.
Pharmacokinetics: Following subcutaneous administration of Cuvitru, peak serum levels are achieved after approximately 3 days.
In a clinical trial with Cuvitru (n=48), the subjects achieved sustained IgG trough levels (median 8.26 g/l) over a period of 52 weeks when receiving median weekly doses of 0.125 g/kg.
Data from the clinical trial of Cuvitru show that serum IgG trough levels can be maintained by dosing regimens of 0.3 to 1.0 g/kg body weight/4 weeks.
The pharmacokinetics of Cuvitru were evaluated in the phase 3 efficacy and safety study in 31 patients with PID aged 12 years and older. The pharmacokinetic results are presented in the following table. (See Table 1.)
Click on icon to see table/diagram/imageIgG and IgG-complexes are broken down in cells of the reticuloendothelial system.
Once Weekly, Biweekly or more Frequent Dosing (2-7 times per week): Pharmacokinetic (PK) characterization of biweekly or more frequent dosing of Cuvitru was undertaken using population PK-based modelling and simulation. Serum IgG concentration data consisted of 724 samples from 32 unique paediatric and adult subjects with PID.
Compared with weekly administration, PK modelling and simulation predicted that administration of Cuvitru on a biweekly basis at double the weekly dose results in overlapping IgG exposure across an entire 2-week interval. In addition, PK modelling and simulation predicted that for the same total weekly dose, Cuvitru infusions given 2-7 times per week (frequent dosing) results also in overlapping IgG exposure across an entire 2-week interval.
Paediatric population: There are no theoretical or observed differences in the pharmacokinetics of immunoglobulins in children compared to adults.
Toxicology: Preclinical safety data: Immune globulins are normal constituents of the human body.
Non-clinical data for immune globulins reveal no special risk for humans based on conventional studies of safety pharmacology and toxicity. Cuvitru was well tolerated locally when infused subcutaneously into animals. Studies of repeated dose toxicity and toxicity to reproduction in animals are impracticable due to induction of and interference by developing antibodies to heterologous proteins.
Long-term animal studies have not been conducted to evaluate the carcinogenic potential of Cuvitru or its effect on fertility. An in vitro mutagenicity test was performed for IGI, 10% and there was no evidence of mutagenicity observed.
