Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties


Pharmacotherapeutic group: immune sera and immunoglobulins: immunoglobulins, normal human, for intravascular administration, ATC code: J06BA02.
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 1,000 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.
GMX01
A phase III, multicentre, non-randomized, open-label study in 50 predominantly adult subjects with primary immunodeficiency diseases (PID), where Gammaplex was infused at a dose of 300 to 800 mg/kg every 21 or 28 days, concluded that Gammaplex was well tolerated and efficacious and therefore suitable for the management of subjects with PID. There were no serious acute bacterial infections during the 12 months of treatment, and the most commonly reported adverse reactions were headache (18 patients), nausea (6 patients), pyrexia (6 patients) and fatigue (6 patients).

GMX02

A later phase III, open-label, multicentre clinical study investigating the safety and efficacy of Gammaplex infused at a dose of 1 g/kg/day for two consecutive days in 35 subjects with chronic immune thrombocytopenic purpura (ITP) showed Gammaplex to be an effective treatment, and hence its efficacy in immunomodulation. The most commonly reported adverse reactions were headache (10 patients), vomiting (6 patients) and pyrexia (5 patients).

Paediatric population

Study GMX01 above, comprised predominantly of adult subjects with PID and included seven patients aged less than 18 years (9-17 years inclusive).
There were no reports of serious adverse reactions in any of the paediatric subjects.

Study GMX02 above in ITP included three subjects aged less than 18 years (6- 17 years inclusive). One of the paediatric subjects (aged six years) experienced a serious adverse reaction (headache, with vomiting and dehydration).

GMX04


A phase III, multicentre, non-randomized, open-label paediatric study in 25 children and adolescent subjects (aged 3-16 years inclusive) with primary immunodeficiency diseases (PID), where Gammaplex was infused at a dose of 300 to 800 mg/kg every 21 or 28 days, concluded that Gammaplex was well tolerated and efficacious in children with PID.
There were two serious acute bacterial infections reported during the 12 months of treatment, and the most commonly reported adverse reactions were headache (8 patients), hypotension (4 patients), pyrexia (3 patients) and tachycardia (3 patients).

Pharmacokinetic Properties

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, and after approximately 3 - 5 days equilibrium is reached between the intra- and extravascular compartments. Human normal immunoglobulin has a half-life of about 31.3 days (range 21.1 days to 42.7 days). This half-life may vary from patient to patient, in particular in primary immunodeficiency.

IgG and IgG-complexes are broken down in cells of the reticuloendothelial system.
Paediatric population

Pharmacokinetic data is available from 25 paediatric patients across the two PID studies: GMX01 (2/50 patients were included in the paediatric PK analysis) and GMX04 (23/25 patients were included in the PK analysis). At steady state Gammaplex was shown to have a median half-life in children of 35.5 days (range 24.2 to 76.2 days).